chr17-19341269-G-A

Variant names:

• chr17-19341269-G-A
• rs190584073
• NM_001321217.2:c.530C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.607

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]

ACMG classification

Verdict is Benign. Variant got -14 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.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00237 (361/152362) while in subpopulation AMR AF= 0.0122 (186/15306). AF 95% confidence interval is 0.0107. There are 2 homozygotes in gnomad4. There are 215 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D1	NM_001321217.2	c.530C>T	p.Ala177Val	missense_variant	Exon 7 of 7		NP_001308146.1
B9D1	NM_001321215.3	c.*2441C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001308144.1
B9D1	XM_047435750.1	c.*2278C>T		3_prime_UTR_variant	Exon 7 of 8		XP_047291706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D1	ENST00000461069.6	c.530C>T	p.Ala177Val	missense_variant	Exon 7 of 7	2		ENSP00000433359.2
B9D1	ENST00000663089	c.*2441C>T		3_prime_UTR_variant	Exon 7 of 7			ENSP00000499469.1
B9D1	ENST00000671102.1	c.535+2521C>T		intron_variant	Intron 7 of 7			ENSP00000499690.1

Frequencies

GnomAD3 genomes AF: 0.00238 AC: 363 AN: 152244 Hom.: 2 Cov.: 32

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.: 2 Cov.: 30 AF XY: 0.000514 AC XY: 262 AN XY: 509614

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.: 2 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74514

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.: 0

Bravo AF: 0.00294

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000246 AC: 2

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

B9D1: BS1 -

B9D1-related disorder Benign:1

Jul 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.5
DANN	Benign	0.36
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0064	T
Sift4G	Uncertain	0.054	T
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

Other links and lift over

dbSNP: rs190584073; hg19: chr17-19244582;