7-85084427-A-T

Variant names:

• chr7-85084427-A-T
• rs12176601
• NM_001384900.1:c.313-2848T>A

Variant summary

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

The NM_001384900.1(SEMA3D):​c.313-2848T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,018 control chromosomes in the GnomAD database, including 5,551 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 0.27 (5551 hom., cov: 32)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 1 publications found

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.313-2848T>A		intron_variant	Intron 4 of 18	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.313-2848T>A		intron_variant	Intron 4 of 18	5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000444867.1	c.313-2848T>A		intron_variant	Intron 4 of 9	1		ENSP00000401366.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40544 AN: 151900 Hom.: 5543 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.267 AC: 40600 AN: 152018 Hom.: 5551 Cov.: 32 AF XY: 0.268 AC XY: 19908 AN XY: 74302

African (AFR) AF: 0.243 AC: 10072 AN: 41476

American (AMR) AF: 0.285 AC: 4349 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3462

East Asian (EAS) AF: 0.380 AC: 1954 AN: 5148

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2354 AN: 10564

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.267 AC: 18147 AN: 67962

Other (OTH) AF: 0.293 AC: 618 AN: 2108

Alfa AF: 0.262 Hom.: 638

Bravo AF: 0.269

Asia WGS AF: 0.355 AC: 1229 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.13
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: rs12176601; hg19: chr7-84713743;