rs7695

Variant names:

• chr1-156177535-T-C
• rs7695
• NM_022367.4:c.*538T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-156177535-T-C
• chr1-156177535-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022367.4(SEMA4A):​c.*538T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 182,336 control chromosomes in the GnomAD database, including 11,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9905 hom., cov: 31)
  • Exomes 𝑓: 0.32 (1845 hom.)
• Consequence: SEMA4A NM_022367.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.51
• Publications: 29 publications found

Genes affected

SEMA4A (HGNC:10729): (semaphorin 4A) This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

SEMA4A Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial colorectal cancer type X

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cone-rod dystrophy 10

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 35

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-156177535-T-C is Benign according to our data. Variant chr1-156177535-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 292867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022367.4. 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
	SEMA4A	NM_022367.4	MANE Select	c.*538T>C		3_prime_UTR	Exon 15 of 15	NP_071762.2
	SEMA4A	NM_001193300.2		c.*538T>C		3_prime_UTR	Exon 16 of 16	NP_001180229.1	Q9H3S1-1
	SEMA4A	NM_001193301.2		c.*538T>C		3_prime_UTR	Exon 15 of 15	NP_001180230.1	Q9H3S1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4A	ENST00000368285.8	TSL:1 MANE Select	c.*538T>C		3_prime_UTR	Exon 15 of 15	ENSP00000357268.3	Q9H3S1-1
	SEMA4A	ENST00000355014.6	TSL:1	c.*538T>C		3_prime_UTR	Exon 15 of 15	ENSP00000347117.2	Q9H3S1-1
	SEMA4A	ENST00000368282.1	TSL:1	c.*538T>C		3_prime_UTR	Exon 14 of 14	ENSP00000357265.1	Q9H3S1-1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53593 AN: 151824 Hom.: 9892 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.321 AC: 9763 AN: 30392 Hom.: 1845 Cov.: 0 AF XY: 0.321 AC XY: 5053 AN XY: 15764

African (AFR) AF: 0.344 AC: 279 AN: 810

American (AMR) AF: 0.279 AC: 949 AN: 3400

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 167 AN: 458

East Asian (EAS) AF: 0.0353 AC: 88 AN: 2496

South Asian (SAS) AF: 0.265 AC: 952 AN: 3596

European-Finnish (FIN) AF: 0.380 AC: 745 AN: 1958

Middle Eastern (MID) AF: 0.441 AC: 30 AN: 68

European-Non Finnish (NFE) AF: 0.373 AC: 6058 AN: 16256

Other (OTH) AF: 0.367 AC: 495 AN: 1350

GnomAD4 genome AF: 0.353 AC: 53635 AN: 151944 Hom.: 9905 Cov.: 31 AF XY: 0.349 AC XY: 25934 AN XY: 74276

African (AFR) AF: 0.337 AC: 13979 AN: 41464

American (AMR) AF: 0.315 AC: 4818 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1355 AN: 3464

East Asian (EAS) AF: 0.0239 AC: 123 AN: 5152

South Asian (SAS) AF: 0.243 AC: 1168 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4241 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26837 AN: 67904

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.378 Hom.: 21928

Bravo AF: 0.344

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 10 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.5
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: rs7695; hg19: chr1-156147326;