7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATAT

Variant names:

• chr7-85055645-CATATATATATATATAT-C
• rs56131427
• NM_001384900.1:c.861+56_861+71delATATATATATATATAT

Variant summary

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

The NM_001384900.1(SEMA3D):​c.861+56_861+71delATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 159,976 control chromosomes in the GnomAD database, including 6,714 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 0.28 (4039 hom., cov: 0)
  • Exomes 𝑓: 0.45 (2675 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 (NFE) allele frequency at 95% confidence interval = 0.324 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+56_861+71delATATATATATATATAT		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.861+56_861+71delATATATATATATATAT		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.861+56_861+71delATATATATATATATAT		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+56_861+71delATATATATATATATAT		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.861+56_861+71delATATATATATATATAT		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.861+56_861+71delATATATATATATATAT		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 30832 AN: 111886 Hom.: 4040 Cov.: 0

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.451 AC: 21697 AN: 48088 Hom.: 2675 AF XY: 0.434 AC XY: 12062 AN XY: 27762

African (AFR) AF: 0.315 AC: 216 AN: 686

American (AMR) AF: 0.335 AC: 259 AN: 772

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 301 AN: 712

East Asian (EAS) AF: 0.159 AC: 163 AN: 1026

South Asian (SAS) AF: 0.376 AC: 384 AN: 1020

European-Finnish (FIN) AF: 0.408 AC: 515 AN: 1262

Middle Eastern (MID) AF: 0.431 AC: 50 AN: 116

European-Non Finnish (NFE) AF: 0.468 AC: 19031 AN: 40634

Other (OTH) AF: 0.418 AC: 778 AN: 1860

GnomAD4 genome AF: 0.276 AC: 30831 AN: 111888 Hom.: 4039 Cov.: 0 AF XY: 0.278 AC XY: 14437 AN XY: 51972

African (AFR) AF: 0.199 AC: 6055 AN: 30418

American (AMR) AF: 0.256 AC: 2461 AN: 9604

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 769 AN: 2954

East Asian (EAS) AF: 0.0894 AC: 322 AN: 3600

South Asian (SAS) AF: 0.197 AC: 591 AN: 2998

European-Finnish (FIN) AF: 0.384 AC: 1413 AN: 3682

Middle Eastern (MID) AF: 0.337 AC: 68 AN: 202

European-Non Finnish (NFE) AF: 0.328 AC: 18449 AN: 56178

Other (OTH) AF: 0.299 AC: 440 AN: 1474

Alfa AF: 0.233 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;