1-151135315-G-A

Position:

• chr1-151135315-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030913.6(SEMA6C):​c.1434-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,612,362 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (10 hom.)
• Consequence: SEMA6C NM_030913.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003026
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0220

Genes affected

SEMA6C (HGNC:10740): (semaphorin 6C) This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-151135315-G-A is Benign according to our data. Variant chr1-151135315-G-A is described in ClinVar as [Benign]. Clinvar id is 717809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00773 (1177/152338) while in subpopulation AFR AF= 0.0271 (1126/41568). AF 95% confidence interval is 0.0258. There are 17 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6C	NM_030913.6	c.1434-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6C	ENST00000368914.8	c.1434-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030913.6	P4

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1174 AN: 152220 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00221 AC: 548 AN: 248016 Hom.: 4 AF XY: 0.00168 AC XY: 225 AN XY: 134022

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000661

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000536

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000773 AC: 1128 AN: 1460024 Hom.: 10 Cov.: 32 AF XY: 0.000693 AC XY: 503 AN XY: 726290

Gnomad4 AFR exome AF: 0.0257

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000513

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00773 AC: 1177 AN: 152338 Hom.: 17 Cov.: 33 AF XY: 0.00752 AC XY: 560 AN XY: 74496

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00458 Hom.: 8

Bravo AF: 0.00909

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs79913209; hg19: chr1-151107791;