7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATAT

Variant names:

• chr7-85055645-CATATATATATATATATAT-C
• rs56131427
• NM_001384900.1:c.861+54_861+71delATATATATATATATATAT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001384900.1(SEMA3D):​c.861+54_861+71delATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 158,472 control chromosomes in the GnomAD database, including 36 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 0.0068 (4 hom., cov: 0)
  • Exomes 𝑓: 0.10 (32 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]

SEMA3D Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	NM_001384900.1	MANE Select	c.861+54_861+71delATATATATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+54_861+71delATATATATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+54_861+71delATATATATATATATATAT		intron	N/A	NP_001371831.1	O95025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.861+54_861+71delATATATATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+54_861+71delATATATATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+54_861+71delATATATATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.00675 AC: 754 AN: 111634 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.000678

Gnomad EAS AF: 0.00221

Gnomad SAS AF: 0.00266

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.0144

Gnomad NFE AF: 0.00633

Gnomad OTH AF: 0.00618

GnomAD4 exome AF: 0.103 AC: 4832 AN: 46836 Hom.: 32 AF XY: 0.101 AC XY: 2736 AN XY: 27076

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

African (AFR) AF: 0.0770 AC: 53 AN: 688

American (AMR) AF: 0.0763 AC: 58 AN: 760

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 66 AN: 688

East Asian (EAS) AF: 0.0244 AC: 25 AN: 1026

South Asian (SAS) AF: 0.0940 AC: 94 AN: 1000

European-Finnish (FIN) AF: 0.0851 AC: 105 AN: 1234

Middle Eastern (MID) AF: 0.152 AC: 17 AN: 112

European-Non Finnish (NFE) AF: 0.107 AC: 4223 AN: 39516

Other (OTH) AF: 0.105 AC: 191 AN: 1812

⚠️ 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: 0.00678 AC: 757 AN: 111636 Hom.: 4 Cov.: 0 AF XY: 0.00675 AC XY: 350 AN XY: 51822

African (AFR) AF: 0.00797 AC: 242 AN: 30382

American (AMR) AF: 0.0125 AC: 120 AN: 9576

Ashkenazi Jewish (ASJ) AF: 0.000678 AC: 2 AN: 2948

East Asian (EAS) AF: 0.00222 AC: 8 AN: 3596

South Asian (SAS) AF: 0.00267 AC: 8 AN: 2992

European-Finnish (FIN) AF: 0.00274 AC: 10 AN: 3644

Middle Eastern (MID) AF: 0.0150 AC: 3 AN: 200

European-Non Finnish (NFE) AF: 0.00633 AC: 355 AN: 56052

Other (OTH) AF: 0.00613 AC: 9 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;