rs78797942

Variant names:

• chr17-19337684-C-A
• rs78797942
• ENST00000671102.1:c.*36G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-19337684-C-A
• chr17-19337684-C-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.*36G>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 0.00431 in 1,529,738 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (278 hom.)
• Consequence: B9D1 NM_001321218.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.442
• Publications: 0 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=-0.75).
• BP6: Variant 17-19337684-C-A is Benign according to our data. Variant chr17-19337684-C-A is described in ClinVar as Benign. ClinVar VariationId is 1175626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.*36G>T		3_prime_UTR	Exon 7 of 7	NP_001308147.1
	B9D1	NM_001321219.2		c.*1G>T		3_prime_UTR	Exon 6 of 6	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.*36G>T		3_prime_UTR	Exon 7 of 7	NP_001355698.1	J3QKN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	ENST00000671102.1		c.*36G>T		3_prime_UTR	Exon 8 of 8	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.*1G>T		3_prime_UTR	Exon 6 of 6	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.*1G>T		3_prime_UTR	Exon 8 of 8	ENSP00000501877.1	A0A6Q8PFN7

Frequencies

GnomAD3 genomes AF: 0.00651 AC: 991 AN: 152236 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.00661

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.0125 AC: 1676 AN: 134344 AF XY: 0.0111

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000228

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00406 AC: 5599 AN: 1377384 Hom.: 278 Cov.: 31 AF XY: 0.00397 AC XY: 2692 AN XY: 678458

African (AFR) AF: 0.000825 AC: 26 AN: 31508

American (AMR) AF: 0.0127 AC: 454 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25128

East Asian (EAS) AF: 0.113 AC: 4018 AN: 35556

South Asian (SAS) AF: 0.00440 AC: 348 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33770

Middle Eastern (MID) AF: 0.000706 AC: 4 AN: 5668

European-Non Finnish (NFE) AF: 0.000249 AC: 267 AN: 1073404

Other (OTH) AF: 0.00837 AC: 482 AN: 57620

GnomAD4 genome AF: 0.00649 AC: 989 AN: 152354 Hom.: 53 Cov.: 32 AF XY: 0.00731 AC XY: 545 AN XY: 74514

African (AFR) AF: 0.00166 AC: 69 AN: 41574

American (AMR) AF: 0.0159 AC: 243 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.118 AC: 612 AN: 5182

South Asian (SAS) AF: 0.00621 AC: 30 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68036

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00209 Hom.: 1

Bravo AF: 0.00737

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.75
CADD	Benign	5.5
DANN	Benign	0.85
PhyloP100		0.44
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: rs78797942; hg19: chr17-19240997; COSMIC: COSV59061349; COSMIC: COSV59061349;