dbSNP rs11096964: FAM114A1:p.Gly84Arg (chr4-38878328-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138389.4(FAM114A1):c.250G>A(p.Gly84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,613,980 control chromosomes in the GnomAD database, including 59,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6118 hom., cov: 33)

Exomes 𝑓: 0.26 ( 53651 hom. )

Consequence

FAM114A1
NM_138389.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

24 publications found

Variant links:

Genes affected

FAM114A1 (HGNC:25087): (family with sequence similarity 114 member A1) The protein encoded by this gene belongs to the FAM114 family and may play a role in neuronal cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

FAM114A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021304488).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A1	NM_138389.4 link	c.250G>A	p.Gly84Arg	missense_variant	Exon 3 of 15	ENST00000358869.5	NP_612398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FAM114A1	ENST00000358869.5 link	c.250G>A	p.Gly84Arg	missense_variant	Exon 3 of 15	1	NM_138389.4	ENSP00000351740.2
FAM114A1	ENST00000510213.5 link	c.250G>A	p.Gly84Arg	missense_variant	Exon 2 of 3	2		ENSP00000422965.1
FAM114A1	ENST00000515037.5 link	c.-274+10494G>A		intron_variant	Intron 1 of 12	2		ENSP00000424115.1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41710

AN:

152076

Hom.:

6096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.0842

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.228

GnomAD2 exomes

AF:

0.250

AC:

62350

AN:

249614

AF XY:

0.241

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.0860

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.265

AC:

387077

AN:

1461786

Hom.:

53651

Cov.:

AF XY:

0.261

AC XY:

189790

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.311

AC:

10409

AN:

33480

American (AMR)

AF:

0.264

AC:

11816

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

5872

AN:

26134

East Asian (EAS)

AF:

0.0732

AC:

2907

AN:

39700

South Asian (SAS)

AF:

0.148

AC:

12739

AN:

86250

European-Finnish (FIN)

AF:

0.350

AC:

18675

AN:

53412

Middle Eastern (MID)

AF:

0.131

AC:

756

AN:

5768

European-Non Finnish (NFE)

AF:

0.277

AC:

308472

AN:

1111950

Other (OTH)

AF:

0.256

AC:

15431

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17060

34119

51179

68238

85298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10130

20260

30390

40520

50650

<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:

0.274

AC:

41773

AN:

152194

Hom.:

6118

Cov.:

AF XY:

0.271

AC XY:

20169

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.311

AC:

12927

AN:

41528

American (AMR)

AF:

0.208

AC:

3183

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

731

AN:

3468

East Asian (EAS)

AF:

0.0847

AC:

440

AN:

5192

South Asian (SAS)

AF:

0.137

AC:

660

AN:

4830

European-Finnish (FIN)

AF:

0.361

AC:

3817

AN:

10568

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19293

AN:

67994

Other (OTH)

AF:

0.233

AC:

492

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.267

Hom.:

19791

Bravo

AF:

0.266

TwinsUK

AF:

0.269

AC:

999

ALSPAC

AF:

0.268

AC:

1033

ESP6500AA

AF:

0.313

AC:

1377

ESP6500EA

AF:

0.273

AC:

2352

ExAC

AF:

0.247

AC:

30048

Asia WGS

AF:

0.165

AC:

574

AN:

3478

EpiCase

AF:

0.265

EpiControl

AF:

0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;N

PhyloP100

1.8

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-7.0

D;N

REVEL

Benign

0.033

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.041

D;T

Vest4

0.0

ClinPred

0.018

GERP RS

1.9

Varity_R

0.040

gMVP

0.12

Mutation Taster

=98/2

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over