7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATAT

Variant names:

• chr7-85055645-CATATATATATATAT-C
• rs56131427
• NM_001384900.1:c.861+58_861+71delATATATATATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384900.1(SEMA3D):​c.861+58_861+71delATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 158,826 control chromosomes in the GnomAD database, including 296 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 0.051 (217 hom., cov: 0)
  • Exomes 𝑓: 0.092 (79 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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

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+58_861+71delATATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+58_861+71delATATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+58_861+71delATATATATATATAT		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+58_861+71delATATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+58_861+71delATATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+58_861+71delATATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 5708 AN: 111646 Hom.: 218 Cov.: 0

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0591

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0433

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0923 AC: 4353 AN: 47178 Hom.: 79 AF XY: 0.0915 AC XY: 2496 AN XY: 27278

African (AFR) AF: 0.114 AC: 78 AN: 682

American (AMR) AF: 0.0792 AC: 61 AN: 770

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 52 AN: 704

East Asian (EAS) AF: 0.274 AC: 283 AN: 1032

South Asian (SAS) AF: 0.0866 AC: 88 AN: 1016

European-Finnish (FIN) AF: 0.0570 AC: 71 AN: 1246

Middle Eastern (MID) AF: 0.0789 AC: 9 AN: 114

European-Non Finnish (NFE) AF: 0.0887 AC: 3530 AN: 39778

Other (OTH) AF: 0.0986 AC: 181 AN: 1836

GnomAD4 genome AF: 0.0511 AC: 5704 AN: 111648 Hom.: 217 Cov.: 0 AF XY: 0.0516 AC XY: 2676 AN XY: 51834

African (AFR) AF: 0.0553 AC: 1681 AN: 30380

American (AMR) AF: 0.0527 AC: 505 AN: 9576

Ashkenazi Jewish (ASJ) AF: 0.0261 AC: 77 AN: 2946

East Asian (EAS) AF: 0.228 AC: 823 AN: 3610

South Asian (SAS) AF: 0.0521 AC: 156 AN: 2994

European-Finnish (FIN) AF: 0.0206 AC: 75 AN: 3644

Middle Eastern (MID) AF: 0.0450 AC: 9 AN: 200

European-Non Finnish (NFE) AF: 0.0402 AC: 2253 AN: 56052

Other (OTH) AF: 0.0538 AC: 79 AN: 1468

Alfa AF: 0.0229 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 (auto)

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;