ENST00000450295:c.*1752C>T

Variant names:

• chr9-89376952-G-A
• rs202211452
• ENST00000450295.5:c.*1752C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000450295.5(SEMA4D):​c.*1752C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,550,636 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (7 hom.)
• Consequence: SEMA4D ENST00000450295.5 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.65
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00844124).
• BP6: Variant 9-89376952-G-A is Benign according to our data. Variant chr9-89376952-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3041927.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450295.5. 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_001142287.2		c.1763C>T	p.Pro588Leu	missense	Exon 18 of 21	NP_001135759.1	Q92854-2
	SEMA4D	NM_001371198.1		c.1763C>T	p.Pro588Leu	missense	Exon 16 of 19	NP_001358127.1	Q92854-2
	SEMA4D	NM_001371199.1		c.1763C>T	p.Pro588Leu	missense	Exon 17 of 20	NP_001358128.1	Q92854-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4D	ENST00000450295.5	TSL:1	c.*1752C>T		3_prime_UTR	Exon 16 of 16	ENSP00000416523.1	Q92854-1
	SEMA4D	ENST00000339861.8	TSL:5	c.1763C>T	p.Pro588Leu	missense	Exon 16 of 19	ENSP00000344923.4	Q92854-2
	SEMA4D	ENST00000420987.5	TSL:5	c.1763C>T	p.Pro588Leu	missense	Exon 17 of 20	ENSP00000391733.1	Q92854-2

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00138 AC: 211 AN: 152964 AF XY: 0.00125

Gnomad AFR exome AF: 0.000653

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000131

Gnomad NFE exome AF: 0.00287

Gnomad OTH exome AF: 0.00323

GnomAD4 exome AF: 0.00264 AC: 3687 AN: 1398332 Hom.: 7 Cov.: 32 AF XY: 0.00255 AC XY: 1760 AN XY: 689676

African (AFR) AF: 0.000348 AC: 11 AN: 31598

American (AMR) AF: 0.00104 AC: 37 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.000145 AC: 7 AN: 48332

Middle Eastern (MID) AF: 0.000704 AC: 4 AN: 5684

European-Non Finnish (NFE) AF: 0.00324 AC: 3500 AN: 1078890

Other (OTH) AF: 0.00214 AC: 124 AN: 57980

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.00121 AC XY: 90 AN XY: 74476

African (AFR) AF: 0.000601 AC: 25 AN: 41574

American (AMR) AF: 0.000718 AC: 11 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00285 AC: 194 AN: 68006

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00275 Hom.: 0

Bravo AF: 0.00162

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00285 AC: 11

ExAC AF: 0.000673 AC: 19

ClinVar

ClinVar submissions

Significance: Likely 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	0.072
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.42
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.021
Sift	Benign	0.12	T
Sift4G	Benign	0.39	T
Polyphen		0.0020	B
Vest4		0.31
MVP		0.068
ClinPred		0.0028	T
GERP RS		0.42
Mutation Taster		=80/20	polymorphism

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: rs202211452; hg19: chr9-91991867;