chr4-146256866-T-C

Position:

• chr4-146256866-T-C

Variant summary

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

The ENST00000507030.5(SLC10A7):​c.1064A>G​(p.Lys355Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,536,246 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (6 hom.)
• Consequence: SLC10A7 ENST00000507030.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.247

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=0.003419578).
• BP6: Variant 4-146256866-T-C is Benign according to our data. Variant chr4-146256866-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2198697.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 = 0.000282 (43/152278) while in subpopulation SAS AF= 0.00417 (20/4798). AF 95% confidence interval is 0.00276. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6	c.994-346A>G		intron_variant		ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000507030.5	c.1064A>G	p.Lys355Arg	missense_variant	12/13	1
SLC10A7	ENST00000335472.12	c.994-346A>G		intron_variant		1	NM_001029998.6	P1
SLC10A7	ENST00000432059.6	c.955-346A>G		intron_variant		1
SLC10A7	ENST00000693222.1	c.1084-346A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00396

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00104 AC: 144 AN: 138632 Hom.: 3 AF XY: 0.00140 AC XY: 105 AN XY: 74822

Gnomad AFR exome AF: 0.000148

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00132

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00494

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.000938

GnomAD4 exome AF: 0.000478 AC: 661 AN: 1383968 Hom.: 6 Cov.: 31 AF XY: 0.000630 AC XY: 430 AN XY: 682904

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.000993

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00520

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.000862

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22 AN XY: 74466

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000684 Hom.: 0

Bravo AF: 0.000230

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00199 AC: 46

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.2
DANN	Benign	0.23
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.022
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.70	T
Vest4		0.080
MutPred		0.20		Loss of ubiquitination at K355 (P = 0.0155);
MVP		0.13
ClinPred		0.0012	T
GERP RS		0.16
gMVP		0.61

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: rs573036097; hg19: chr4-147178018;