17-19337659-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000671102.1(B9D1):c.*61C>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 0.969 in 1,502,002 control chromosomes in the GnomAD database, including 708,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71418 hom., cov: 34)
  • Exomes 𝑓: 0.97 (636898 hom.)
• Consequence: B9D1 ENST00000671102.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-19337659-G-A is Benign according to our data. Variant chr17-19337659-G-A is described in ClinVar as [Benign]. Clinvar id is 1192493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D1	NM_001321218.2	c.*61C>T		3_prime_UTR_variant	7/7
B9D1	NM_001321219.2	c.*26C>T		3_prime_UTR_variant	6/6
B9D1	NM_001368769.2	c.*61C>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D1	ENST00000582857.2	c.*61C>T		3_prime_UTR_variant	7/7	4
B9D1	ENST00000671102.1	c.*61C>T		3_prime_UTR_variant	8/8
B9D1	ENST00000674596.1	c.*26C>T		3_prime_UTR_variant	8/8
B9D1	ENST00000675510.1	c.*26C>T		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147131 AN: 152214 Hom.: 71371 Cov.: 34

Gnomad AFR AF: 0.991

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.969

GnomAD3 exomes AF: 0.905 AC: 121376 AN: 134102 Hom.: 55664 AF XY: 0.906 AC XY: 66186 AN XY: 73064

Gnomad AFR exome AF: 0.991

Gnomad AMR exome AF: 0.772

Gnomad ASJ exome AF: 0.987

Gnomad EAS exome AF: 0.835

Gnomad SAS exome AF: 0.804

Gnomad FIN exome AF: 0.986

Gnomad NFE exome AF: 0.989

Gnomad OTH exome AF: 0.945

GnomAD4 exome AF: 0.970 AC: 1308766 AN: 1349670 Hom.: 636898 Cov.: 23 AF XY: 0.965 AC XY: 641159 AN XY: 664218

Gnomad4 AFR exome AF: 0.993

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.986

Gnomad4 EAS exome AF: 0.863

Gnomad4 SAS exome AF: 0.810

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.990

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.967 AC: 147235 AN: 152332 Hom.: 71418 Cov.: 34 AF XY: 0.960 AC XY: 71539 AN XY: 74488

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.969

Alfa AF: 0.978 Hom.: 64922

Bravo AF: 0.962

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Joubert syndrome 27 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Meckel syndrome, type 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.59
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11652712; hg19: chr17-19240972;