Genetic Variant B9D1:c.-129+166T>A (chr17-19377693-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000674596.1(B9D1):c.-129+166T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

B9D1
ENST00000674596.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

8 publications found

Variant links:

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 links:

MAPK7 (HGNC:6880): (mitogen-activated protein kinase 7) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MAPK7 links:

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ACMG classification

Classification was made for transcript

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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
B9D1	NM_001368769.2 link	c.-298+166T>A	intron_variant	Intron 1 of 6	NP_001355698.1
B9D1	XM_047435750.1 link	c.-96+166T>A	intron_variant	Intron 1 of 7	XP_047291706.1
B9D1	XM_047435751.1 link	c.-1456+166T>A	intron_variant	Intron 1 of 10	XP_047291707.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
B9D1	ENST00000674596.1 link	c.-129+166T>A	intron_variant	Intron 1 of 7		ENSP00000501877.1	A0A6Q8PFN7
B9D1	ENST00000642870.2 link	c.-298+166T>A	intron_variant	Intron 1 of 6		ENSP00000496409.2	A0A2R8Y822
B9D1	ENST00000477478.7 link	c.-298+166T>A	intron_variant	Intron 1 of 5	3	ENSP00000460939.2	I3L435

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

107984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51652

African (AFR)

AF:

0.00

AC:

AN:

2214

American (AMR)

AF:

0.00

AC:

AN:

116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

672

East Asian (EAS)

AF:

0.00

AC:

AN:

426

South Asian (SAS)

AF:

0.00

AC:

AN:

2138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

98680

Other (OTH)

AF:

0.00

AC:

AN:

3476

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

(source)

DANN

Benign

0.30

PhyloP100

-1.3

PromoterAI

-0.068

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over