4-146294038-T-C

Position:

• chr4-146294038-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001029998.6(SLC10A7):​c.613A>G​(p.Ile205Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000655 in 1,611,170 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (12 hom.)
• Consequence: SLC10A7 NM_001029998.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.292

Genes affected

SLC10A7 (HGNC:23088): (solute carrier family 10 member 7) Enables bile acid transmembrane transporter activity. Involved in several processes, including cellular calcium ion homeostasis; glycoprotein transport; and heparin biosynthetic process. Located in Golgi apparatus and endoplasmic reticulum. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065972507).
• BP6: Variant 4-146294038-T-C is Benign according to our data. Variant chr4-146294038-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2198698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000355 (54/152032) while in subpopulation SAS AF= 0.0056 (27/4818). AF 95% confidence interval is 0.00395. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6	c.613A>G	p.Ile205Val	missense_variant	8/12	ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000335472.12	c.613A>G	p.Ile205Val	missense_variant	8/12	1	NM_001029998.6	P1

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 151912 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00121 AC: 303 AN: 250086 Hom.: 5 AF XY: 0.00160 AC XY: 216 AN XY: 135158

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000205

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00814

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000686 AC: 1001 AN: 1459138 Hom.: 12 Cov.: 31 AF XY: 0.000925 AC XY: 671 AN XY: 725780

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.000997

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00798

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30 AN XY: 74344

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000357 Hom.: 0

Bravo AF: 0.000268

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00132 AC: 160

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	SLC10A7: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 14, 2023	- -

SLC10A7-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.22
DANN	Benign	0.52
DEOGEN2	Benign	0.0092	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.77	T;T;T
MetaRNN	Benign	0.0066	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.82	.;L;L
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.56	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.12
MVP		0.030
MPC		0.34
ClinPred		0.0064	T
GERP RS		-5.7
Varity_R		0.014
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs201948152; hg19: chr4-147215190;