17-19338052-C-T

Variant names:

• chr17-19338052-C-T
• rs72838804
• ENST00000671102.1:c.536-304G>A

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.473-304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00854 in 152,298 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0085 (9 hom., cov: 34)
• Consequence: B9D1 NM_001321218.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.292
• Publications: 3 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=-0.82).
• BP6: Variant 17-19338052-C-T is Benign according to our data. Variant chr17-19338052-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1197455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00854 (1301/152298) while in subpopulation SAS AF = 0.0234 (113/4828). AF 95% confidence interval is 0.0199. There are 9 homozygotes in GnomAd4. There are 610 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.473-304G>A		intron	N/A	NP_001308147.1
	B9D1	NM_001321219.2		c.405-304G>A		intron	N/A	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.113-304G>A		intron	N/A	NP_001355698.1	J3QKN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	ENST00000671102.1		c.536-304G>A		intron	N/A	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.405-304G>A		intron	N/A	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.303-304G>A		intron	N/A	ENSP00000501877.1	A0A6Q8PFN7

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1300 AN: 152182 Hom.: 9 Cov.: 34

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.00854 AC: 1301 AN: 152298 Hom.: 9 Cov.: 34 AF XY: 0.00819 AC XY: 610 AN XY: 74474

African (AFR) AF: 0.00255 AC: 106 AN: 41554

American (AMR) AF: 0.00732 AC: 112 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3462

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4828

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 814 AN: 68016

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00917 Hom.: 1

Bravo AF: 0.00848

Asia WGS AF: 0.0120 AC: 41 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	-0.82
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.29
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: rs72838804; hg19: chr17-19241365;