chr5-102249735-G-A

Variant names:

• chr5-102249735-G-A
• rs529284686
• NM_180991.5:c.1523C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_180991.5(SLCO4C1):​c.1523C>T​(p.Ser508Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SLCO4C1 NM_180991.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012419194).
• BP6: Variant 5-102249735-G-A is Benign according to our data. Variant chr5-102249735-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3320389.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5	c.1523C>T	p.Ser508Leu	missense_variant	Exon 9 of 13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3	c.1259C>T	p.Ser420Leu	missense_variant	Exon 8 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2	c.1109C>T	p.Ser370Leu	missense_variant	Exon 11 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1	c.1109C>T	p.Ser370Leu	missense_variant	Exon 11 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.1523C>T	p.Ser508Leu	missense_variant	Exon 9 of 13	1	NM_180991.5	ENSP00000309741.6

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000638 AC: 16 AN: 250860 AF XY: 0.0000885

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461634 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727118

African (AFR) AF: 0.000478 AC: 16 AN: 33470

American (AMR) AF: 0.000157 AC: 7 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111882

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74390

African (AFR) AF: 0.000746 AC: 31 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.000253

ExAC AF: 0.0000988 AC: 12

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.60
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.10	N
PhyloP100		1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.077
Sift	Benign	0.92	T
Sift4G	Benign	0.41	T
Polyphen		0.0030	B
Vest4		0.15
MVP		0.14
MPC		0.039
ClinPred		0.0096	T
GERP RS		4.5
Varity_R		0.040
gMVP		0.33
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs529284686; hg19: chr5-101585439; COSMIC: COSV60520631;