chr1-112526029-C-T

Position:

• chr1-112526029-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017744.5(ST7L):​c.1712G>A​(p.Gly571Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 1,614,136 control chromosomes in the GnomAD database, including 458 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.030 (253 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (205 hom.)
• Consequence: ST7L NM_017744.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133

Genes affected

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016414523).
• BP6: Variant 1-112526029-C-T is Benign according to our data. Variant chr1-112526029-C-T is described in ClinVar as [Benign]. Clinvar id is 767688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7L	NM_017744.5	c.1712G>A	p.Gly571Asp	missense_variant	15/15	ENST00000358039.9
WNT2B	NM_024494.3	c.*5520C>T		3_prime_UTR_variant	5/5	ENST00000369684.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7L	ENST00000358039.9	c.1712G>A	p.Gly571Asp	missense_variant	15/15	1	NM_017744.5
WNT2B	ENST00000369684.5	c.*5520C>T		3_prime_UTR_variant	5/5	1	NM_024494.3	P1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4593 AN: 152144 Hom.: 253 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00818 AC: 2037 AN: 248912 Hom.: 93 AF XY: 0.00570 AC XY: 768 AN XY: 134748

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.00526

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000288

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00307 AC: 4486 AN: 1461874 Hom.: 205 Cov.: 31 AF XY: 0.00256 AC XY: 1865 AN XY: 727240

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00599

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.00709

GnomAD4 genome AF: 0.0302 AC: 4604 AN: 152262 Hom.: 253 Cov.: 32 AF XY: 0.0295 AC XY: 2200 AN XY: 74454

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00520 Hom.: 59

Bravo AF: 0.0344

ESP6500AA AF: 0.100 AC: 441

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00998 AC: 1212

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000593

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

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.55	T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.0	B;B;.;B
Vest4		0.16
MVP		0.27
MPC		0.51
ClinPred		0.042	T
GERP RS		1.9
Varity_R		0.19
gMVP		0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12069022; hg19: chr1-113068651;