1-151134828-C-G

Variant names:

• chr1-151134828-C-G
• rs74127528
• NM_030913.6:c.1628G>C

Variant summary

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

The NM_030913.6(SEMA6C):​c.1628G>C​(p.Arg543Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,614,184 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (102 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (116 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0370

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017738342).
• BP6: Variant 1-151134828-C-G is Benign according to our data. Variant chr1-151134828-C-G is described in ClinVar as [Benign]. Clinvar id is 767698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6C	NM_030913.6	c.1628G>C	p.Arg543Thr	missense_variant	Exon 16 of 19	ENST00000368914.8	NP_112175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6C	ENST00000368914.8	c.1628G>C	p.Arg543Thr	missense_variant	Exon 16 of 19	1	NM_030913.6	ENSP00000357910.3

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3200 AN: 152200 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00565 AC: 1421 AN: 251472 AF XY: 0.00411

Gnomad AFR exome AF: 0.0779

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00219 AC: 3208 AN: 1461866 Hom.: 116 Cov.: 32 AF XY: 0.00189 AC XY: 1371 AN XY: 727238

Gnomad4 AFR exome AF: 0.0772 AC: 2585 AN: 33476

Gnomad4 AMR exome AF: 0.00385 AC: 172 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000174 AC: 15 AN: 86256

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53420

Gnomad4 NFE exome AF: 0.000129 AC: 143 AN: 1111996

Gnomad4 Remaining exome AF: 0.00449 AC: 271 AN: 60394

GnomAD4 genome AF: 0.0211 AC: 3209 AN: 152318 Hom.: 102 Cov.: 32 AF XY: 0.0207 AC XY: 1542 AN XY: 74482

Gnomad4 AFR AF: 0.0725 AC: 0.0724945 AN: 0.0724945

Gnomad4 AMR AF: 0.00993 AC: 0.00992945 AN: 0.00992945

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207039 AN: 0.000207039

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000176 AC: 0.000176408 AN: 0.000176408

Gnomad4 OTH AF: 0.0142 AC: 0.0141911 AN: 0.0141911

Alfa AF: 0.00160 Hom.: 5

Bravo AF: 0.0242

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0794 AC: 350

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00703 AC: 854

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.054	.;.;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.82	T;T;.;D
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.12	T;T;T;T
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		0.013	B;B;B;B
Vest4		0.50
MVP		0.66
MPC		0.97
ClinPred		0.015	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.087
gMVP		0.47
Mutation Taster		=97/3	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74127528; hg19: chr1-151107304;