7-85055645-CATATATATATATATATATATATATATATAT-CATATATAT

Variant names:

• chr7-85055645-CATATATATATATATATATATAT-C
• rs56131427
• NM_001384900.1:c.861+50_861+71delATATATATATATATATATATAT

Variant summary

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

The NM_001384900.1(SEMA3D):​c.861+50_861+71delATATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 159,792 control chromosomes in the GnomAD database, including 6 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 0.0031 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (3 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00197 (95/48148) while in subpopulation AFR AF = 0.042 (29/690). AF 95% confidence interval is 0.0301. There are 3 homozygotes in GnomAdExome4. There are 45 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 351 AD 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+50_861+71delATATATATATATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+50_861+71delATATATATATATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+50_861+71delATATATATATATATATATATAT		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+50_861+71delATATATATATATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+50_861+71delATATATATATATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+50_861+71delATATATATATATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 351 AN: 111642 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000553

Gnomad SAS AF: 0.00133

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00481

Gnomad NFE AF: 0.000268

Gnomad OTH AF: 0.000687

GnomAD4 exome AF: 0.00197 AC: 95 AN: 48148 Hom.: 3 AF XY: 0.00162 AC XY: 45 AN XY: 27800

African (AFR) AF: 0.0420 AC: 29 AN: 690

American (AMR) AF: 0.00258 AC: 2 AN: 774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 710

East Asian (EAS) AF: 0.00193 AC: 2 AN: 1038

South Asian (SAS) AF: 0.00977 AC: 10 AN: 1024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1262

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

European-Non Finnish (NFE) AF: 0.00113 AC: 46 AN: 40672

Other (OTH) AF: 0.00323 AC: 6 AN: 1860

GnomAD4 genome AF: 0.00314 AC: 351 AN: 111644 Hom.: 3 Cov.: 0 AF XY: 0.00322 AC XY: 167 AN XY: 51824

African (AFR) AF: 0.0103 AC: 314 AN: 30382

American (AMR) AF: 0.00146 AC: 14 AN: 9572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2948

East Asian (EAS) AF: 0.000556 AC: 2 AN: 3598

South Asian (SAS) AF: 0.00134 AC: 4 AN: 2992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3644

Middle Eastern (MID) AF: 0.00500 AC: 1 AN: 200

European-Non Finnish (NFE) AF: 0.000268 AC: 15 AN: 56062

Other (OTH) AF: 0.000681 AC: 1 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

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;