Variant chr17-19341269-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001321217.2(B9D1):c.530C>T(p.Ala177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,231,900 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 2 hom. )

Consequence

B9D1
NM_001321217.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.607

Variant links:

Genes affected

B9D1 (HGNC:24123): (B9 domain containing 1) This gene encodes a B9 domain-containing protein, one of several that are involved in ciliogenesis. Alterations in expression of this gene have been found in a family with Meckel syndrome. Meckel syndrome has been associated with at least six different genes. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Mar 2016]

B9D1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006423712).

BP6

Variant 17-19341269-G-A is Benign according to our data. Variant chr17-19341269-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024937.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
B9D1	NM_001321217.2 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	7/7	NP_001308146.1
B9D1	NM_001321215.3 linkuse as main transcript	c.*2441C>T		3_prime_UTR_variant	6/6	NP_001308144.1
B9D1	XM_047435750.1 linkuse as main transcript	c.*2278C>T		3_prime_UTR_variant	7/8	XP_047291706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein
B9D1	ENST00000461069.6 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	7/7	2	ENSP00000433359
B9D1	ENST00000663089.1 linkuse as main transcript	c.*2441C>T		3_prime_UTR_variant	7/7		ENSP00000499469
B9D1	ENST00000582857.2 linkuse as main transcript	c.112+2521C>T		intron_variant		4	ENSP00000463165

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

363

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00997

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00622

GnomAD4 exome

AF:

0.000541

AC:

584

AN:

1079538

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

262

AN XY:

509614

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.000347

Gnomad4 EAS exome

AF:

0.000565

Gnomad4 SAS exome

AF:

0.00221

Gnomad4 FIN exome

AF:

0.00948

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152362

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00997

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00294

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000246

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

Feb 01, 2024

B9D1: BS1 -

B9D1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.5

DANN

Benign

0.36

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0064

MutationTaster

Benign

1.0

N;N

Sift4G

Uncertain

0.054

Vest4

0.11

MVP

0.82

GERP RS

-0.61

Splicing

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