NM_001371194.2:c.2484G>A

Variant names:

• chr9-89378809-C-T
• rs45483393
• NM_001371194.2:c.2484G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001371194.2(SEMA4D):​c.2484G>A​(p.Thr828Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,614,110 control chromosomes in the GnomAD database, including 1,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.041 (179 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1452 hom.)
• Consequence: SEMA4D NM_001371194.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.51
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-89378809-C-T is Benign according to our data. Variant chr9-89378809-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056145.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371194.2. 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
	SEMA4D	NM_001371194.2	MANE Select	c.2484G>A	p.Thr828Thr	synonymous	Exon 16 of 16	NP_001358123.1	Q92854-1
	SEMA4D	NM_001371195.1		c.2484G>A	p.Thr828Thr	synonymous	Exon 17 of 17	NP_001358124.1	Q92854-1
	SEMA4D	NM_001371196.1		c.2484G>A	p.Thr828Thr	synonymous	Exon 18 of 18	NP_001358125.1	Q92854-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4D	ENST00000422704.7	TSL:1 MANE Select	c.2484G>A	p.Thr828Thr	synonymous	Exon 16 of 16	ENSP00000388768.2	Q92854-1
	SEMA4D	ENST00000438547.6	TSL:1	c.2484G>A	p.Thr828Thr	synonymous	Exon 18 of 18	ENSP00000405102.2	Q92854-1
	SEMA4D	ENST00000450295.5	TSL:1	c.2484G>A	p.Thr828Thr	synonymous	Exon 16 of 16	ENSP00000416523.1	Q92854-1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6229 AN: 152132 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0409 AC: 10292 AN: 251434 AF XY: 0.0430

Gnomad AFR exome AF: 0.0599

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.0902

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0327

GnomAD4 exome AF: 0.0362 AC: 52973 AN: 1461860 Hom.: 1452 Cov.: 32 AF XY: 0.0380 AC XY: 27607 AN XY: 727238

African (AFR) AF: 0.0602 AC: 2015 AN: 33480

American (AMR) AF: 0.0159 AC: 710 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 580 AN: 26136

East Asian (EAS) AF: 0.128 AC: 5086 AN: 39698

South Asian (SAS) AF: 0.0909 AC: 7843 AN: 86256

European-Finnish (FIN) AF: 0.0235 AC: 1257 AN: 53412

Middle Eastern (MID) AF: 0.0250 AC: 144 AN: 5768

European-Non Finnish (NFE) AF: 0.0296 AC: 32894 AN: 1111992

Other (OTH) AF: 0.0405 AC: 2444 AN: 60394

GnomAD4 genome AF: 0.0409 AC: 6232 AN: 152250 Hom.: 179 Cov.: 33 AF XY: 0.0411 AC XY: 3056 AN XY: 74444

African (AFR) AF: 0.0583 AC: 2420 AN: 41528

American (AMR) AF: 0.0243 AC: 372 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.0952 AC: 492 AN: 5166

South Asian (SAS) AF: 0.0971 AC: 469 AN: 4828

European-Finnish (FIN) AF: 0.0221 AC: 235 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2055 AN: 68020

Other (OTH) AF: 0.0341 AC: 72 AN: 2112

Alfa AF: 0.0352 Hom.: 254

Bravo AF: 0.0407

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA4D-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.19
DANN	Benign	0.61
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs45483393; hg19: chr9-91993724; COSMIC: COSV59391786; COSMIC: COSV59391786;