NM_180991.5:c.2173T>C

Variant names:

• chr5-102236860-A-G
• rs144705663
• NM_180991.5:c.2173T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_180991.5(SLCO4C1):​c.2173T>C​(p.Ter725Argext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.000496 in 1,610,390 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (4 hom.)
• Consequence: SLCO4C1 NM_180991.5 stop_lost
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.36
• Publications: 5 publications found

Genes affected

SLCO4C1 (HGNC:23612): (solute carrier organic anion transporter family member 4C1) SLCO4C1 belongs to the organic anion transporter (OATP) family. OATPs are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues (Mikkaichi et al., 2004 [PubMed 14993604]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• PM4: Stoplost variant in NM_180991.5 Downstream stopcodon found after 14 codons.
• BP6: Variant 5-102236860-A-G is Benign according to our data. Variant chr5-102236860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 727471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5	c.2173T>C	p.Ter725Argext*?	stop_lost	Exon 13 of 13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3	c.1909T>C	p.Ter637Argext*?	stop_lost	Exon 12 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2	c.1759T>C	p.Ter587Argext*?	stop_lost	Exon 15 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1	c.1759T>C	p.Ter587Argext*?	stop_lost	Exon 15 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.2173T>C	p.Ter725Argext*?	stop_lost	Exon 13 of 13	1	NM_180991.5	ENSP00000309741.6

Frequencies

GnomAD3 genomes AF: 0.000290 AC: 44 AN: 151904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000802 AC: 199 AN: 248172 AF XY: 0.00104

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000518 AC: 755 AN: 1458368 Hom.: 4 Cov.: 31 AF XY: 0.000659 AC XY: 478 AN XY: 725232

African (AFR) AF: 0.0000300 AC: 1 AN: 33364

American (AMR) AF: 0.000362 AC: 16 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00533 AC: 453 AN: 85044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52988

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5750

European-Non Finnish (NFE) AF: 0.000232 AC: 258 AN: 1111128

Other (OTH) AF: 0.000299 AC: 18 AN: 60296

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74318

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.000197 AC: 3 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00416 AC: 20 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000166

ExAC AF: 0.000865 AC: 105

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000383

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.76
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.73	D
PhyloP100		4.4
Vest4		0.0050
GERP RS		4.7
Mutation Taster		=152/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs144705663; hg19: chr5-101572564;