9-89402909-C-T

Variant names:

• chr9-89402909-C-T
• rs13284404
• NM_001371194.2:c.214G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001371194.2(SEMA4D):​c.214G>A​(p.Ala72Thr) variant causes a missense change. The variant allele was found at a frequency of 0.045 in 1,613,980 control chromosomes in the GnomAD database, including 1,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.034 (127 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1818 hom.)
• Consequence: SEMA4D NM_001371194.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.47
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010484457).
• BP6: Variant 9-89402909-C-T is Benign according to our data. Variant chr9-89402909-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055397.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 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.214G>A	p.Ala72Thr	missense	Exon 4 of 16	NP_001358123.1	Q92854-1
	SEMA4D	NM_001371195.1		c.214G>A	p.Ala72Thr	missense	Exon 5 of 17	NP_001358124.1	Q92854-1
	SEMA4D	NM_001371196.1		c.214G>A	p.Ala72Thr	missense	Exon 6 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.214G>A	p.Ala72Thr	missense	Exon 4 of 16	ENSP00000388768.2	Q92854-1
	SEMA4D	ENST00000438547.6	TSL:1	c.214G>A	p.Ala72Thr	missense	Exon 6 of 18	ENSP00000405102.2	Q92854-1
	SEMA4D	ENST00000450295.5	TSL:1	c.214G>A	p.Ala72Thr	missense	Exon 4 of 16	ENSP00000416523.1	Q92854-1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5103 AN: 152128 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00893

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0357 AC: 8970 AN: 251412 AF XY: 0.0359

Gnomad AFR exome AF: 0.00812

Gnomad AMR exome AF: 0.0315

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0724

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0380

GnomAD4 exome AF: 0.0462 AC: 67480 AN: 1461734 Hom.: 1818 Cov.: 32 AF XY: 0.0453 AC XY: 32908 AN XY: 727148

African (AFR) AF: 0.00654 AC: 219 AN: 33480

American (AMR) AF: 0.0311 AC: 1392 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 345 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0188 AC: 1623 AN: 86258

European-Finnish (FIN) AF: 0.0726 AC: 3878 AN: 53388

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.0519 AC: 57693 AN: 1111896

Other (OTH) AF: 0.0377 AC: 2277 AN: 60388

GnomAD4 genome AF: 0.0335 AC: 5106 AN: 152246 Hom.: 127 Cov.: 32 AF XY: 0.0342 AC XY: 2542 AN XY: 74428

African (AFR) AF: 0.00890 AC: 370 AN: 41550

American (AMR) AF: 0.0321 AC: 492 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4824

European-Finnish (FIN) AF: 0.0751 AC: 795 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0475 AC: 3228 AN: 68014

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0401 Hom.: 496

Bravo AF: 0.0294

TwinsUK AF: 0.0491 AC: 182

ALSPAC AF: 0.0490 AC: 189

ESP6500AA AF: 0.00794 AC: 35

ESP6500EA AF: 0.0435 AC: 374

ExAC AF: 0.0340 AC: 4134

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0410

EpiControl AF: 0.0431

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
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.5
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.72	P
Vest4		0.36
MPC		0.65
ClinPred		0.049	T
GERP RS		4.8
Varity_R		0.77
gMVP		0.50
Mutation Taster		=98/2	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: rs13284404; hg19: chr9-92017824; COSMIC: COSV59392573; COSMIC: COSV59392573;