17-19337684-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000671102.1(B9D1):c.*36G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,529,738 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (278 hom.)
• Consequence: B9D1 ENST00000671102.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.442

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 (BayesDel_noAF=-0.75).
• BP6: Variant 17-19337684-C-A is Benign according to our data. Variant chr17-19337684-C-A is described in ClinVar as [Benign]. Clinvar id is 1175626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D1	NM_001321218.2	c.*36G>T		3_prime_UTR_variant	7/7
B9D1	NM_001321219.2	c.*1G>T		3_prime_UTR_variant	6/6
B9D1	NM_001368769.2	c.*36G>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D1	ENST00000582857.2	c.*36G>T		3_prime_UTR_variant	7/7	4
B9D1	ENST00000671102.1	c.*36G>T		3_prime_UTR_variant	8/8
B9D1	ENST00000674596.1	c.*1G>T		3_prime_UTR_variant	8/8
B9D1	ENST00000675510.1	c.*1G>T		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.00651 AC: 991 AN: 152236 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.00661

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.0125 AC: 1676 AN: 134344 Hom.: 75 AF XY: 0.0111 AC XY: 814 AN XY: 73184

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.00378

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000228

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00406 AC: 5599 AN: 1377384 Hom.: 278 Cov.: 31 AF XY: 0.00397 AC XY: 2692 AN XY: 678458

Gnomad4 AFR exome AF: 0.000825

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.00440

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000249

Gnomad4 OTH exome AF: 0.00837

GnomAD4 genome AF: 0.00649 AC: 989 AN: 152354 Hom.: 53 Cov.: 32 AF XY: 0.00731 AC XY: 545 AN XY: 74514

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00209 Hom.: 1

Bravo AF: 0.00737

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.5
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78797942; hg19: chr17-19240997; COSMIC: COSV59061349; COSMIC: COSV59061349;