Variant 8-138148521-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_015912.4(FAM135B):c.3447T>C(p.Asp1149Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,613,646 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0062 ( 40 hom. )

Consequence

FAM135B
NM_015912.4 splice_region, synonymous

Scores

Splicing: ADA: 0.01413

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

FAM135B (HGNC:28029): (family with sequence similarity 135 member B) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

FAM135B links:

FAM135B (HGNC:):

FAM135B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-138148521-A-G is Benign according to our data. Variant chr8-138148521-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658847.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00622 (9095/1461354) while in subpopulation MID AF= 0.0229 (132/5766). AF 95% confidence interval is 0.0197. There are 40 homozygotes in gnomad4_exome. There are 4469 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM135B	NM_015912.4 linkuse as main transcript	c.3447T>C	p.Asp1149Asp	splice_region_variant, synonymous_variant	14/20	ENST00000395297.6	NP_056996.2	Q49AJ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM135B	ENST00000395297.6 linkuse as main transcript	c.3447T>C	p.Asp1149Asp	splice_region_variant, synonymous_variant	14/20	5	NM_015912.4	ENSP00000378710.1		Q49AJ0-1

Frequencies

GnomAD3 genomes

AF:

0.00519

AC:

790

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00685

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00547

AC:

1374

AN:

251110

Hom.:

AF XY:

0.00549

AC XY:

745

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00983

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00622

AC:

9095

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

4469

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.00645

Gnomad4 OTH exome

AF:

0.00692

GnomAD4 genome

AF:

0.00518

AC:

789

AN:

152292

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.00685

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.00462

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00803

EpiControl

AF:

0.00622

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

FAM135B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

3.3

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over