rs181754797

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-19337906-T-C
• chr17-19337906-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 27

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Meckel syndrome, type 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Genomics England PanelApp
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321218.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	NM_001321218.2		c.473-158A>G		intron	N/A	NP_001308147.1
	B9D1	NM_001321219.2		c.405-158A>G		intron	N/A	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.113-158A>G		intron	N/A	NP_001355698.1	J3QKN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	ENST00000671102.1		c.536-158A>G		intron	N/A	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.405-158A>G		intron	N/A	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.303-158A>G		intron	N/A	ENSP00000501877.1	A0A6Q8PFN7

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

African (AFR) AF: 0.0132 AC: 506 AN: 38422

American (AMR) AF: 0.00141 AC: 20 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4810

South Asian (SAS) AF: 0.00 AC: 0 AN: 4494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9214

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.0000913 AC: 6 AN: 65690

Other (OTH) AF: 0.00305 AC: 6 AN: 1964

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00406

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs181754797; hg19: chr17-19241219;