17-19337684-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321218.2(B9D1):​c.*36G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,377,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: B9D1 NM_001321218.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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>C		3_prime_UTR	Exon 7 of 7	NP_001308147.1
	B9D1	NM_001321219.2		c.*1G>C		3_prime_UTR	Exon 6 of 6	NP_001308148.1	A0A6Q8PFJ7
	B9D1	NM_001368769.2		c.*36G>C		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>C		3_prime_UTR	Exon 8 of 8	ENSP00000499690.1	A0A590UK40
	B9D1	ENST00000675510.1		c.*1G>C		3_prime_UTR	Exon 6 of 6	ENSP00000501817.1	A0A6Q8PFJ7
	B9D1	ENST00000674596.1		c.*1G>C		3_prime_UTR	Exon 8 of 8	ENSP00000501877.1	A0A6Q8PFN7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1377396 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678462

African (AFR) AF: 0.00 AC: 0 AN: 31508

American (AMR) AF: 0.00 AC: 0 AN: 35620

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35564

South Asian (SAS) AF: 0.00 AC: 0 AN: 79110

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1073404

Other (OTH) AF: 0.00 AC: 0 AN: 57624

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		0.44

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;