Genetic Variant FAM107B:p.Leu271Val (chr10-14521300-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031453.4(FAM107B):c.811C>G(p.Leu271Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,814 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

FAM107B
NM_031453.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.35

Publications

2 publications found

Variant links:

Genes affected

FAM107B (HGNC:23726): (family with sequence similarity 107 member B) Predicted to act upstream of or within sensory perception of sound. [provided by Alliance of Genome Resources, Apr 2022]

FAM107B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046301186).

BP6

Variant 10-14521300-G-C is Benign according to our data. Variant chr10-14521300-G-C is described in ClinVar as Benign. ClinVar VariationId is 785307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1916/152286) while in subpopulation AFR AF = 0.0431 (1793/41554). AF 95% confidence interval is 0.0415. There are 38 homozygotes in GnomAd4. There are 895 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031453.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM107B	NM_031453.4	MANE Select	c.811C>G	p.Leu271Val	missense	Exon 5 of 5	NP_113641.2
FAM107B	NM_001320741.2		c.403C>G	p.Leu135Val	missense	Exon 4 of 4	NP_001307670.1
FAM107B	NM_001282695.2		c.286C>G	p.Leu96Val	missense	Exon 6 of 6	NP_001269624.1	Q9H098-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM107B	ENST00000181796.7	TSL:2 MANE Select	c.811C>G	p.Leu271Val	missense	Exon 5 of 5	ENSP00000181796.2	Q9H098-2
FAM107B	ENST00000378467.8	TSL:1	c.286C>G	p.Leu96Val	missense	Exon 5 of 5	ENSP00000367728.4	Q9H098-1
FAM107B	ENST00000378470.5	TSL:1	c.286C>G	p.Leu96Val	missense	Exon 4 of 4	ENSP00000367731.1	Q9H098-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1911

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00815

GnomAD2 exomes

AF:

0.00336

AC:

843

AN:

250842

AF XY:

0.00262

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00132

AC:

1935

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

810

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.0469

AC:

1568

AN:

33462

American (AMR)

AF:

0.00313

AC:

140

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000693

AC:

AN:

1111800

Other (OTH)

AF:

0.00224

AC:

135

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

189

283

378

472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0126

AC:

1916

AN:

152286

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

895

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0431

AC:

1793

AN:

41554

American (AMR)

AF:

0.00628

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68028

Other (OTH)

AF:

0.00806

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.0147

ESP6500AA

AF:

0.0409

AC:

180

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00376

AC:

456

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

3.4

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.78

REVEL

Benign

0.094

Sift

Benign

0.082

Sift4G

Benign

0.17

Polyphen

0.55

Vest4

0.33

MVP

0.44

MPC

0.61

ClinPred

0.027

GERP RS

5.6

Varity_R

0.15

gMVP

0.060

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over