7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATAT

Variant names:

• chr7-85055645-CATATATATATAT-C
• rs56131427
• NM_001384900.1:c.861+60_861+71delATATATATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001384900.1(SEMA3D):​c.861+60_861+71delATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 159,668 control chromosomes in the GnomAD database, including 31 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (30 hom., cov: 0)
  • Exomes 𝑓: 0.0092 (1 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0156 (1745/111636) while in subpopulation AFR AF = 0.0425 (1292/30380). AF 95% confidence interval is 0.0406. There are 30 homozygotes in GnomAd4. There are 833 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	NM_001384900.1	MANE Select	c.861+60_861+71delATATATATATAT		intron	N/A	NP_001371829.1
	SEMA3D	NM_001384901.1		c.861+60_861+71delATATATATATAT		intron	N/A	NP_001371830.1
	SEMA3D	NM_001384902.1		c.861+60_861+71delATATATATATAT		intron	N/A	NP_001371831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.861+60_861+71delATATATATATAT		intron	N/A	ENSP00000284136.6
	SEMA3D	ENST00000444867.1	TSL:1	c.861+60_861+71delATATATATATAT		intron	N/A	ENSP00000401366.1
	SEMA3D	ENST00000463315.1	TSL:2	n.49+60_49+71delATATATATATAT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 1741 AN: 111634 Hom.: 30 Cov.: 0

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00522

Gnomad ASJ AF: 0.0142

Gnomad EAS AF: 0.0393

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00893

GnomAD4 exome AF: 0.00922 AC: 443 AN: 48032 Hom.: 1 AF XY: 0.00951 AC XY: 264 AN XY: 27750

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0465 AC: 32 AN: 688

American (AMR) AF: 0.0142 AC: 11 AN: 772

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 14 AN: 710

East Asian (EAS) AF: 0.0512 AC: 53 AN: 1036

South Asian (SAS) AF: 0.00786 AC: 8 AN: 1018

European-Finnish (FIN) AF: 0.0206 AC: 26 AN: 1260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 118

European-Non Finnish (NFE) AF: 0.00675 AC: 274 AN: 40572

Other (OTH) AF: 0.0135 AC: 25 AN: 1858

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0156 AC: 1745 AN: 111636 Hom.: 30 Cov.: 0 AF XY: 0.0161 AC XY: 833 AN XY: 51820

African (AFR) AF: 0.0425 AC: 1292 AN: 30380

American (AMR) AF: 0.00522 AC: 50 AN: 9570

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 42 AN: 2948

East Asian (EAS) AF: 0.0395 AC: 142 AN: 3594

South Asian (SAS) AF: 0.00334 AC: 10 AN: 2992

European-Finnish (FIN) AF: 0.0140 AC: 51 AN: 3644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.00259 AC: 145 AN: 56062

Other (OTH) AF: 0.00886 AC: 13 AN: 1468

Alfa AF: 0.00 Hom.: 173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56131427; hg19: chr7-84684961;