17-19337906-T-C

Variant names:

• chr17-19337906-T-C
• rs181754797
• ENST00000671102.1:c.536-158A>G

Variant summary

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

The NM_001321218.2(B9D1):​c.473-158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 143,340 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0038 (4 hom., cov: 32)
• Consequence: B9D1 NM_001321218.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.174

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=-0.87).
• BP6: Variant 17-19337906-T-C is Benign according to our data. Variant chr17-19337906-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00376 (539/143340) while in subpopulation AFR AF= 0.0132 (506/38422). AF 95% confidence interval is 0.0122. There are 4 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D1	NM_001321218.2	c.473-158A>G		intron_variant	Intron 6 of 6		NP_001308147.1
B9D1	NM_001321219.2	c.405-158A>G		intron_variant	Intron 5 of 5		NP_001308148.1
B9D1	NM_001368769.2	c.113-158A>G		intron_variant	Intron 6 of 6		NP_001355698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D1	ENST00000671102.1	c.536-158A>G		intron_variant	Intron 7 of 7			ENSP00000499690.1
B9D1	ENST00000675510.1	c.405-158A>G		intron_variant	Intron 5 of 5			ENSP00000501817.1
B9D1	ENST00000674596.1	c.303-158A>G		intron_variant	Intron 7 of 7			ENSP00000501877.1
B9D1	ENST00000582857.2	c.113-158A>G		intron_variant	Intron 6 of 6	4		ENSP00000463165.2

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 538 AN: 143268 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0000913

Gnomad OTH AF: 0.00309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00376 AC: 539 AN: 143340 Hom.: 4 Cov.: 32 AF XY: 0.00378 AC XY: 263 AN XY: 69604

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000913

Gnomad4 OTH AF: 0.00305

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00406

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 14, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs181754797; hg19: chr17-19241219;