chr17-19338052-C-T

Variant names:

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

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.473-304G>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

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=-0.82).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D1	NM_001321218.2	c.473-304G>A		intron_variant	Intron 6 of 6		NP_001308147.1
B9D1	NM_001321219.2	c.405-304G>A		intron_variant	Intron 5 of 5		NP_001308148.1
B9D1	NM_001368769.2	c.113-304G>A		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.536-304G>A		intron_variant	Intron 7 of 7			ENSP00000499690.1
B9D1	ENST00000675510.1	c.405-304G>A		intron_variant	Intron 5 of 5			ENSP00000501817.1
B9D1	ENST00000674596.1	c.303-304G>A		intron_variant	Intron 7 of 7			ENSP00000501877.1
B9D1	ENST00000582857.2	c.113-304G>A		intron_variant	Intron 6 of 6	4		ENSP00000463165.2

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

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00917 Hom.: 1

Bravo AF: 0.00848

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72838804; hg19: chr17-19241365;