rs4774497

Variant names:

• chr15-47566058-G-A
• rs4774497
• ENST00000558014.5:c.-86-34807G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47566058-G-A
• chr15-47566058-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558014.5(SEMA6D):​c.-86-34807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,144 control chromosomes in the GnomAD database, including 15,482 homozygotes. 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: 𝑓 0.43 (15482 hom., cov: 33)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849
• Publications: 3 publications found

Genes affected

SEMA6D (HGNC:16770): (semaphorin 6D) Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. This gene encodes a class 6 vertebrate transmembrane semaphorin that demonstrates alternative splicing. Several transcript variants have been identified and expression of the distinct encoded isoforms is thought to be regulated in a tissue- and development-dependent manner. [provided by RefSeq, Nov 2010]

SEMA6D Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-34807G>A		intron_variant	Intron 3 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-86-34807G>A		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-34807G>A		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-34807G>A		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65587 AN: 152026 Hom.: 15479 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65610 AN: 152144 Hom.: 15482 Cov.: 33 AF XY: 0.434 AC XY: 32270 AN XY: 74380

African (AFR) AF: 0.258 AC: 10696 AN: 41504

American (AMR) AF: 0.376 AC: 5740 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1159 AN: 5182

South Asian (SAS) AF: 0.521 AC: 2506 AN: 4808

European-Finnish (FIN) AF: 0.582 AC: 6157 AN: 10580

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36092 AN: 68012

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.483 Hom.: 13923

Bravo AF: 0.400

Asia WGS AF: 0.367 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.0
DANN	Benign	0.62
PhyloP100		0.85
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4774497; hg19: chr15-47858255;