7-83367517-G-GATTT

Position:

• chr7-83367517-G-GATTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012431.3(SEMA3E):​c.*68_*69insAAAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,486,050 control chromosomes in the GnomAD database, including 1,630 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (898 hom., cov: 31)
  • Exomes 𝑓: 0.0060 (732 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206

Genes affected

SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-83367517-G-GATTT is Benign according to our data. Variant chr7-83367517-G-GATTT is described in ClinVar as [Benign]. Clinvar id is 1236886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.*68_*69insAAAT		3_prime_UTR_variant	17/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.*68_*69insAAAT		3_prime_UTR_variant	17/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*68_*69insAAAT		3_prime_UTR_variant	17/17		NM_012431.3	ENSP00000496491	P1
SEMA3E	ENST00000643441.1	n.2381_2382insAAAT		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9106 AN: 151964 Hom.: 897 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.00604 AC: 8058 AN: 1333968 Hom.: 732 Cov.: 22 AF XY: 0.00523 AC XY: 3508 AN XY: 670602

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000481

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000354

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0601 AC: 9137 AN: 152082 Hom.: 898 Cov.: 31 AF XY: 0.0576 AC XY: 4281 AN XY: 74360

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0536 Hom.: 37

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5885345; hg19: chr7-82996833;