rs4871880

Positions:

• chr8-23536059-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000519973.6(SLC25A37):​c.210+6847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,154 control chromosomes in the GnomAD database, including 1,556 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 0.12 (1556 hom., cov: 32)
• Consequence: SLC25A37 ENST00000519973.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

Genes affected

SLC25A37 (HGNC:29786): (solute carrier family 25 member 37) SLC25A37 is a solute carrier localized in the mitochondrial inner membrane. It functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters (summary by Chen et al., 2009 [PubMed 19805291]).[supplied by OMIM, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.210+6847G>A		intron_variant		ENST00000519973.6	NP_057696.2
SLC25A37	NM_001317812.2	c.-721+6847G>A		intron_variant			NP_001304741.1
SLC25A37	NM_001317813.2	c.-131+6847G>A		intron_variant			NP_001304742.1
SLC25A37	NM_001317814.2	c.-77-775G>A		intron_variant			NP_001304743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6	c.210+6847G>A		intron_variant		1	NM_016612.4	ENSP00000429200	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18695 AN: 152036 Hom.: 1552 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.123 AC: 18706 AN: 152154 Hom.: 1556 Cov.: 32 AF XY: 0.124 AC XY: 9223 AN XY: 74398

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.149

Alfa AF: 0.143 Hom.: 497

Bravo AF: 0.130

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.66

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: rs4871880; hg19: chr8-23393572;