12-47779569-T-C

Variant names:

• chr12-47779569-T-C
• rs4760636
• NM_017842.3:c.304+374T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017842.3(SLC48A1):​c.304+374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,076 control chromosomes in the GnomAD database, including 47,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47211 hom., cov: 31)
• Consequence: SLC48A1 NM_017842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 15 publications found

Genes affected

SLC48A1 (HGNC:26035): (solute carrier family 48 member 1) Enables heme binding activity and heme transmembrane transporter activity. Involved in heme transport. Located in endosome membrane; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC48A1	NM_017842.3	c.304+374T>C		intron_variant	Intron 2 of 2	ENST00000442218.3	NP_060312.2
SLC48A1	XM_047429134.1	c.418+374T>C		intron_variant	Intron 4 of 5		XP_047285090.1
SLC48A1	XM_005269016.4	c.385+374T>C		intron_variant	Intron 3 of 3		XP_005269073.1
SLC48A1	XM_017019617.3	c.304+374T>C		intron_variant	Intron 2 of 3		XP_016875106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC48A1	ENST00000442218.3	c.304+374T>C		intron_variant	Intron 2 of 2	1	NM_017842.3	ENSP00000415998.2
SLC48A1	ENST00000442892.2	c.133+374T>C		intron_variant	Intron 3 of 4	1		ENSP00000410134.2
SLC48A1	ENST00000551301.1	n.*141+374T>C		intron_variant	Intron 2 of 2	2		ENSP00000449036.1
SLC48A1	ENST00000547002.5	c.133+374T>C		intron_variant	Intron 4 of 4	3		ENSP00000446739.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119439 AN: 151958 Hom.: 47152 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.786 AC: 119559 AN: 152076 Hom.: 47211 Cov.: 31 AF XY: 0.786 AC XY: 58370 AN XY: 74308

African (AFR) AF: 0.809 AC: 33573 AN: 41480

American (AMR) AF: 0.777 AC: 11884 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2480 AN: 3462

East Asian (EAS) AF: 0.922 AC: 4764 AN: 5166

South Asian (SAS) AF: 0.798 AC: 3850 AN: 4826

European-Finnish (FIN) AF: 0.775 AC: 8192 AN: 10570

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52227 AN: 67958

Other (OTH) AF: 0.784 AC: 1659 AN: 2116

Alfa AF: 0.774 Hom.: 82156

Bravo AF: 0.791

Asia WGS AF: 0.861 AC: 2997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs4760636; hg19: chr12-48173352;