chr6-31671193-C-T

Variant names:

• chr6-31671193-C-T
• rs141943810
• ENST00000409525:c.-70C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000409525(LY6G5B):​c.-70C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000936 in 1,613,968 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (25 hom.)
• Consequence: LY6G5B ENST00000409525 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

Genes affected

LY6G5B (HGNC:13931): (lymphocyte antigen 6 family member G5B) LY6G5B belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

ENSG00000263020 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006375611).
• BP6: Variant 6-31671193-C-T is Benign according to our data. Variant chr6-31671193-C-T is described in ClinVar as [Benign]. Clinvar id is 732236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000946 (144/152246) while in subpopulation EAS AF = 0.027 (140/5184). AF 95% confidence interval is 0.0234. There are 1 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G5B	NM_021221.3	c.96C>T	p.Leu32Leu	synonymous_variant	Exon 2 of 3	ENST00000375864.5	NP_067044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000263020	ENST00000375880.6	c.595C>T	p.Arg199Cys	missense_variant	Exon 7 of 8	3		ENSP00000365040.2
LY6G5B	ENST00000375864.5	c.96C>T	p.Leu32Leu	synonymous_variant	Exon 2 of 3	1	NM_021221.3	ENSP00000365024.4

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00224 AC: 558 AN: 248938 AF XY: 0.00199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.0296

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000935 AC: 1366 AN: 1461722 Hom.: 25 Cov.: 31 AF XY: 0.000899 AC XY: 654 AN XY: 727168

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33480

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44724

Gnomad4 ASJ exome AF: 0.0000765 AC: 2 AN: 26130

Gnomad4 EAS exome AF: 0.0328 AC: 1302 AN: 39700

Gnomad4 SAS exome AF: 0.000255 AC: 22 AN: 86256

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53396

Gnomad4 NFE exome AF: 0.00000809 AC: 9 AN: 1111882

Gnomad4 Remaining exome AF: 0.000513 AC: 31 AN: 60392

GnomAD4 genome AF: 0.000946 AC: 144 AN: 152246 Hom.: 1 Cov.: 32 AF XY: 0.000994 AC XY: 74 AN XY: 74448

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0270 AC: 0.0270062 AN: 0.0270062

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000441 AC: 0.0000441151 AN: 0.0000441151

Gnomad4 OTH AF: 0.000474 AC: 0.000474383 AN: 0.000474383

Alfa AF: 0.0000820 Hom.: 0

Bravo AF: 0.00162

ExAC AF: 0.00201 AC: 244

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	12
DANN	Uncertain	1.0
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.022
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.14	T
Vest4		0.32
MVP		0.42
MPC		1.7
ClinPred		0.079	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs141943810; hg19: chr6-31638970;