chr7-83367515-A-T

Variant names:

• chr7-83367515-A-T
• rs75164403
• NM_012431.3:c.*71T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012431.3(SEMA3E):​c.*71T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,464,550 control chromosomes in the GnomAD database, including 10,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (827 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9545 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.637
• Publications: 7 publications found

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]

SEMA3E Gene-Disease associations (from GenCC):

• CHD7-related CHARGE syndrome

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• CHARGE syndrome

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Kallmann syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-83367515-A-T is Benign according to our data. Variant chr7-83367515-A-T is described in ClinVar as Benign. ClinVar VariationId is 1291034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012431.3. 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
	SEMA3E	NM_012431.3	MANE Select	c.*71T>A		3_prime_UTR	Exon 17 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.*71T>A		3_prime_UTR	Exon 17 of 17	NP_001171600.1	O15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	ENST00000643230.2	MANE Select	c.*71T>A		3_prime_UTR	Exon 17 of 17	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000643441.1		n.2384T>A		non_coding_transcript_exon	Exon 17 of 17
	SEMA3E	ENST00000891111.1		c.*71T>A		downstream_gene	N/A	ENSP00000561170.1

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14141 AN: 148712 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.116 AC: 153011 AN: 1315724 Hom.: 9545 Cov.: 20 AF XY: 0.118 AC XY: 78471 AN XY: 662806

African (AFR) AF: 0.0217 AC: 565 AN: 26060

American (AMR) AF: 0.154 AC: 6820 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.0973 AC: 2458 AN: 25256

East Asian (EAS) AF: 0.102 AC: 3978 AN: 39052

South Asian (SAS) AF: 0.173 AC: 14334 AN: 82918

European-Finnish (FIN) AF: 0.0918 AC: 4896 AN: 53334

Middle Eastern (MID) AF: 0.183 AC: 1004 AN: 5474

European-Non Finnish (NFE) AF: 0.114 AC: 112416 AN: 984042

Other (OTH) AF: 0.118 AC: 6540 AN: 55370

GnomAD4 genome AF: 0.0951 AC: 14146 AN: 148826 Hom.: 827 Cov.: 32 AF XY: 0.0976 AC XY: 7112 AN XY: 72842

African (AFR) AF: 0.0249 AC: 953 AN: 38296

American (AMR) AF: 0.144 AC: 2191 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3464

East Asian (EAS) AF: 0.133 AC: 689 AN: 5168

South Asian (SAS) AF: 0.168 AC: 808 AN: 4814

European-Finnish (FIN) AF: 0.0952 AC: 1009 AN: 10600

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7723 AN: 67990

Other (OTH) AF: 0.117 AC: 244 AN: 2090

Alfa AF: 0.0937 Hom.: 92

Bravo AF: 0.0923

Asia WGS AF: 0.133 AC: 461 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs75164403; hg19: chr7-82996831;