ENST00000671102.1:c.536-34T>C

Variant names:

• chr17-19337782-A-G
• rs72836802
• ENST00000671102.1:c.536-34T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000671102.1(B9D1):​c.536-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 1,469,554 control chromosomes in the GnomAD database, including 3,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (222 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2820 hom.)
• Consequence: B9D1 ENST00000671102.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-19337782-A-G is Benign according to our data. Variant chr17-19337782-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000671102.1. 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.473-34T>C		intron	N/A	NP_001308147.1
	B9D1	NM_001321219.2		c.405-34T>C		intron	N/A	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.113-34T>C		intron	N/A	NP_001355698.1	J3QKN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	ENST00000671102.1		c.536-34T>C		intron	N/A	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.405-34T>C		intron	N/A	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.303-34T>C		intron	N/A	ENSP00000501877.1	A0A6Q8PFN7

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7280 AN: 151742 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0725

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0560

GnomAD2 exomes AF: 0.0689 AC: 9213 AN: 133806 AF XY: 0.0716

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0556

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0621 AC: 81777 AN: 1317694 Hom.: 2820 Cov.: 22 AF XY: 0.0633 AC XY: 41246 AN XY: 652090

African (AFR) AF: 0.0171 AC: 514 AN: 30036

American (AMR) AF: 0.0606 AC: 2124 AN: 35040

Ashkenazi Jewish (ASJ) AF: 0.0776 AC: 1882 AN: 24240

East Asian (EAS) AF: 0.120 AC: 4134 AN: 34472

South Asian (SAS) AF: 0.101 AC: 7935 AN: 78178

European-Finnish (FIN) AF: 0.0364 AC: 1168 AN: 32118

Middle Eastern (MID) AF: 0.0973 AC: 528 AN: 5428

European-Non Finnish (NFE) AF: 0.0585 AC: 59840 AN: 1023062

Other (OTH) AF: 0.0663 AC: 3652 AN: 55120

GnomAD4 genome AF: 0.0480 AC: 7294 AN: 151860 Hom.: 222 Cov.: 32 AF XY: 0.0487 AC XY: 3617 AN XY: 74248

African (AFR) AF: 0.0174 AC: 722 AN: 41518

American (AMR) AF: 0.0544 AC: 831 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 251 AN: 3462

East Asian (EAS) AF: 0.113 AC: 581 AN: 5138

South Asian (SAS) AF: 0.0992 AC: 476 AN: 4800

European-Finnish (FIN) AF: 0.0378 AC: 396 AN: 10480

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3860 AN: 67880

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0529 Hom.: 44

Bravo AF: 0.0486

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs72836802; hg19: chr17-19241095;