rs3866958

chr17-19377693-A-Cchr17-19377693-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000674596.1(B9D1):c.-129+166T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 260,162 control chromosomes in the GnomAD database, including 113,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (61414 hom., cov: 33)
  • Exomes 𝑓: 0.98 (51837 hom.)
• Consequence: B9D1 ENST00000674596.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-19377693-A-C is Benign according to our data. Variant chr17-19377693-A-C is described in ClinVar as [Benign]. Clinvar id is 1178285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D1	NM_001368769.2	c.-298+166T>G		intron_variant
B9D1	XM_005256610.3	c.-1456+166T>G		intron_variant
B9D1	XM_047435750.1	c.-96+166T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D1	ENST00000477478.7	c.-298+166T>G		intron_variant		3
B9D1	ENST00000582857.2	c.-298+166T>G		intron_variant		4
B9D1	ENST00000642870.2	c.-298+166T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135425 AN: 152118 Hom.: 61371 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.918

GnomAD4 exome AF: 0.979 AC: 105617 AN: 107926 Hom.: 51837 Cov.: 4 AF XY: 0.979 AC XY: 50549 AN XY: 51616

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.845

Gnomad4 ASJ exome AF: 0.985

Gnomad4 EAS exome AF: 0.850

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.947

GnomAD4 genome AF: 0.890 AC: 135524 AN: 152236 Hom.: 61414 Cov.: 33 AF XY: 0.887 AC XY: 66010 AN XY: 74434

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.988

Gnomad4 OTH AF: 0.919

Alfa AF: 0.914 Hom.: 12262

Bravo AF: 0.876

Asia WGS AF: 0.834 AC: 2901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

This variant is associated with the following publications: (PMID: 23804708) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3866958; hg19: chr17-19281006;