rs2726953

Positions:

• chr8-27943788-G-A
• chr8-27943788-G-C

Variant summary

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

The NM_173833.6(SCARA5):​c.242-21543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,058 control chromosomes in the GnomAD database, including 5,504 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 0.27 (5504 hom., cov: 32)
• Consequence: SCARA5 NM_173833.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

Genes affected

SCARA5 (HGNC:28701): (scavenger receptor class A member 5) Predicted to enable ferritin receptor activity. Predicted to be involved in several processes, including cellular iron ion homeostasis; iron ion transmembrane transport; and protein homotrimerization. Predicted to act upstream of or within cellular response to heat. Predicted to be located in cell surface. Predicted to be integral component of plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA5	NM_173833.6	c.242-21543C>T		intron_variant		ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1	c.113-21543C>T		intron_variant			NP_001400130.1
SCARA5	NM_001413202.1	c.242-21543C>T		intron_variant			NP_001400131.1
SCARA5	NM_001413203.1	c.-563-21543C>T		intron_variant			NP_001400132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA5	ENST00000354914.8	c.242-21543C>T		intron_variant		2	NM_173833.6	ENSP00000346990.3
SCARA5	ENST00000524352.5	c.242-21543C>T		intron_variant		1		ENSP00000428663.1
SCARA5	ENST00000518030.1	c.113-21543C>T		intron_variant		1		ENSP00000430713.1
SCARA5	ENST00000380385.6	c.241+22626C>T		intron_variant		1		ENSP00000369746.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40378 AN: 151940 Hom.: 5506 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.266 AC: 40397 AN: 152058 Hom.: 5504 Cov.: 32 AF XY: 0.266 AC XY: 19807 AN XY: 74328

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.259

Alfa AF: 0.191 Hom.: 494

Bravo AF: 0.260

Asia WGS AF: 0.294 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.9
DANN	Benign	0.73

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: rs2726953; hg19: chr8-27801305;