17-19337782-A-G

Position:

• chr17-19337782-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000671102.1(B9D1):​c.536-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 1,469,554 control chromosomes in the GnomAD database, including 3,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (222 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2820 hom.)
• Consequence: B9D1 ENST00000671102.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-19337782-A-G is Benign according to our data. Variant chr17-19337782-A-G is described in ClinVar as [Benign]. Clinvar id is 1222802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D1	NM_001321218.2	c.473-34T>C		intron_variant
B9D1	NM_001321219.2	c.405-34T>C		intron_variant
B9D1	NM_001368769.2	c.113-34T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D1	ENST00000582857.2	c.113-34T>C		intron_variant		4
B9D1	ENST00000671102.1	c.536-34T>C		intron_variant
B9D1	ENST00000674596.1	c.303-34T>C		intron_variant
B9D1	ENST00000675510.1	c.405-34T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7280 AN: 151742 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0725

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0560

GnomAD3 exomes AF: 0.0689 AC: 9213 AN: 133806 Hom.: 384 AF XY: 0.0716 AC XY: 5229 AN XY: 73006

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.121

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0556

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0621 AC: 81777 AN: 1317694 Hom.: 2820 Cov.: 22 AF XY: 0.0633 AC XY: 41246 AN XY: 652090

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0606

Gnomad4 ASJ exome AF: 0.0776

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0364

Gnomad4 NFE exome AF: 0.0585

Gnomad4 OTH exome AF: 0.0663

GnomAD4 genome AF: 0.0480 AC: 7294 AN: 151860 Hom.: 222 Cov.: 32 AF XY: 0.0487 AC XY: 3617 AN XY: 74248

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0725

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0529 Hom.: 44

Bravo AF: 0.0486

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72836802; hg19: chr17-19241095;