Genetic Variant NM_173348.2:c.1128-83T>C (chr10-73232856-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_173348.2(FAM149B1):c.1128-83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 819,028 control chromosomes in the GnomAD database, including 4,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 624 hom., cov: 32)

Exomes 𝑓: 0.086 ( 3995 hom. )

Consequence

FAM149B1
NM_173348.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

4 publications found

Variant links:

Genes affected

FAM149B1 (HGNC:29162): (family with sequence similarity 149 member B1) Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

FAM149B1 links:

DNAJC9 (HGNC:19123): (DnaJ heat shock protein family (Hsp40) member C9) Enables chaperone binding activity; heat shock protein binding activity; and histone binding activity. Involved in nucleosome assembly and positive regulation of ATPase activity. Located in several cellular components, including cytosol; extracellular space; and nucleoplasm. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC9 links:

ENSG00000310418 (HGNC:):

ENSG00000310418 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM149B1	NM_173348.2	MANE Select	c.1128-83T>C		intron	N/A	NP_775483.1	Q96BN6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM149B1	ENST00000242505.11	TSL:5 MANE Select	c.1128-83T>C	intron	N/A	ENSP00000242505.6	Q96BN6-1
FAM149B1	ENST00000372955.7	TSL:1	c.924-83T>C	intron	N/A	ENSP00000362046.3	H7BY93
FAM149B1	ENST00000959965.1		c.1122-83T>C	intron	N/A	ENSP00000630024.1

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10531

AN:

152174

Hom.:

625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0714

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0416

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0617

GnomAD4 exome

AF:

0.0864

AC:

57593

AN:

666736

Hom.:

3995

AF XY:

0.0927

AC XY:

32469

AN XY:

350192

show subpopulations

African (AFR)

AF:

0.0459

AC:

786

AN:

17110

American (AMR)

AF:

0.0775

AC:

2419

AN:

31204

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

1847

AN:

19404

East Asian (EAS)

AF:

0.284

AC:

9156

AN:

32288

South Asian (SAS)

AF:

0.212

AC:

12935

AN:

60978

European-Finnish (FIN)

AF:

0.0451

AC:

1994

AN:

44216

Middle Eastern (MID)

AF:

0.0448

AC:

139

AN:

3102

European-Non Finnish (NFE)

AF:

0.0602

AC:

25575

AN:

424658

Other (OTH)

AF:

0.0812

AC:

2742

AN:

33776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2562

5123

7685

10246

12808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.0692

AC:

10542

AN:

152292

Hom.:

624

Cov.:

AF XY:

0.0718

AC XY:

5347

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0433

AC:

1800

AN:

41560

American (AMR)

AF:

0.0715

AC:

1094

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0922

AC:

320

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1592

AN:

5182

South Asian (SAS)

AF:

0.217

AC:

1044

AN:

4820

European-Finnish (FIN)

AF:

0.0416

AC:

441

AN:

10610

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0589

AC:

4010

AN:

68024

Other (OTH)

AF:

0.0649

AC:

137

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

495

990

1485

1980

2475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0629

Hom.:

Bravo

AF:

0.0680

Asia WGS

AF:

0.241

AC:

838

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.2

(source)

DANN

Benign

0.64

PhyloP100

-0.15

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over