17-19337913-T-C

Variant names:

• chr17-19337913-T-C
• rs11650112
• ENST00000671102.1:c.536-165A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001321218.2(B9D1):​c.473-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 151,084 control chromosomes in the GnomAD database, including 70,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.97 (70880 hom., cov: 26)
• Consequence: B9D1 NM_001321218.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52
• 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=-0.89).
• BP6: Variant 17-19337913-T-C is Benign according to our data. Variant chr17-19337913-T-C is described in ClinVar as Benign. ClinVar VariationId is 1292519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

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.473-165A>G		intron	N/A	NP_001308147.1
	B9D1	NM_001321219.2		c.405-165A>G		intron	N/A	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.113-165A>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.536-165A>G		intron	N/A	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.405-165A>G		intron	N/A	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.303-165A>G		intron	N/A	ENSP00000501877.1	A0A6Q8PFN7

Frequencies

GnomAD3 genomes AF: 0.967 AC: 146052 AN: 150972 Hom.: 70834 Cov.: 26

Gnomad AFR AF: 0.991

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.967 AC: 146154 AN: 151084 Hom.: 70880 Cov.: 26 AF XY: 0.961 AC XY: 70879 AN XY: 73722

African (AFR) AF: 0.990 AC: 40788 AN: 41184

American (AMR) AF: 0.877 AC: 13284 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3435 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4296 AN: 5028

South Asian (SAS) AF: 0.815 AC: 3841 AN: 4714

European-Finnish (FIN) AF: 0.983 AC: 10204 AN: 10380

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67077 AN: 67854

Other (OTH) AF: 0.968 AC: 2033 AN: 2100

Alfa AF: 0.965 Hom.: 25047

Bravo AF: 0.962

Asia WGS AF: 0.847 AC: 2943 AN: 3476

ClinVar

ClinVar submissions

Significance: 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	-0.89
CADD	Benign	0.50
DANN	Benign	0.42
PhyloP100		-2.5
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: rs11650112; hg19: chr17-19241226;