rs1555607998

Variant names:

• chr17-19347822-T-A
• rs1555607998
• NM_015681.6:c.303A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_015681.6(B9D1):​c.303A>T​(p.Arg101Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: B9D1 NM_015681.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.799
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048623115).
• BP6: Variant 17-19347822-T-A is Benign according to our data. Variant chr17-19347822-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 461760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.799 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015681.6. 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_015681.6	MANE Select	c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 7	NP_056496.1	Q9UPM9-1
	B9D1	NM_001321214.2		c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 7	NP_001308143.1	A8MYG7
	B9D1	NM_001321217.2		c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 7	NP_001308146.1	A0A0B4J223

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D1	ENST00000261499.11	TSL:1 MANE Select	c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 7	ENSP00000261499.4	Q9UPM9-1
	B9D1	ENST00000268841.10	TSL:1	c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 6	ENSP00000268841.6	Q9UPM9-2
	B9D1	ENST00000477683.5	TSL:1	c.303A>T	p.Arg101Arg	synonymous	Exon 4 of 5	ENSP00000494660.1	A0A2R8Y5M4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.4
DANN	Benign	0.83
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.049	T
PhyloP100		-0.80
PrimateAI	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Vest4		0.36
MVP		0.68
GERP RS		-1.1
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1555607998; hg19: chr17-19251135;