rs4132699

Variant names:

• chr9-89421512-A-C
• rs4132699
• NM_001371194.2:c.-243-15813T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-89421512-A-C
• chr9-89421512-A-G
• chr9-89421512-A-T

Variant summary

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

The NM_001371194.2(SEMA4D):​c.-243-15813T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,016 control chromosomes in the GnomAD database, including 13,940 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 0.42 (13940 hom., cov: 32)
• Consequence: SEMA4D NM_001371194.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 12 publications found

Genes affected

SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4D	NM_001371194.2	c.-243-15813T>G		intron_variant	Intron 2 of 15	ENST00000422704.7	NP_001358123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4D	ENST00000422704.7	c.-243-15813T>G		intron_variant	Intron 2 of 15	1	NM_001371194.2	ENSP00000388768.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64262 AN: 151898 Hom.: 13910 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.423 AC: 64326 AN: 152016 Hom.: 13940 Cov.: 32 AF XY: 0.419 AC XY: 31106 AN XY: 74280

African (AFR) AF: 0.517 AC: 21406 AN: 41440

American (AMR) AF: 0.323 AC: 4938 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2194 AN: 5174

South Asian (SAS) AF: 0.309 AC: 1490 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4022 AN: 10538

Middle Eastern (MID) AF: 0.545 AC: 158 AN: 290

European-Non Finnish (NFE) AF: 0.400 AC: 27227 AN: 67994

Other (OTH) AF: 0.402 AC: 850 AN: 2112

Alfa AF: 0.400 Hom.: 42800

Bravo AF: 0.425

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4132699; hg19: chr9-92036427;