8-27872010-C-T

Position:

• chr8-27872010-C-T

Variant summary

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

The NM_173833.6(SCARA5):​c.1412G>A​(p.Arg471His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,614,194 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (134 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (125 hom.)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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 (MetaRNN=0.0024001002).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA5	NM_173833.6	c.1412G>A	p.Arg471His	missense_variant	9/9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1	c.1283G>A	p.Arg428His	missense_variant	8/8		NP_001400130.1
SCARA5	NM_001413203.1	c.608G>A	p.Arg203His	missense_variant	8/8		NP_001400132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA5	ENST00000354914.8	c.1412G>A	p.Arg471His	missense_variant	9/9	2	NM_173833.6	ENSP00000346990.3
SCARA5	ENST00000380385.6	c.737G>A	p.Arg246His	missense_variant	8/8	1		ENSP00000369746.2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3520 AN: 152204 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00636 AC: 1589 AN: 249740 Hom.: 53 AF XY: 0.00473 AC XY: 639 AN XY: 135114

Gnomad AFR exome AF: 0.0818

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000580

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00260 AC: 3806 AN: 1461872 Hom.: 125 Cov.: 33 AF XY: 0.00223 AC XY: 1619 AN XY: 727236

Gnomad4 AFR exome AF: 0.0795

Gnomad4 AMR exome AF: 0.00537

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000430

Gnomad4 OTH exome AF: 0.00601

GnomAD4 genome AF: 0.0232 AC: 3529 AN: 152322 Hom.: 134 Cov.: 33 AF XY: 0.0231 AC XY: 1724 AN XY: 74486

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.00895

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.00449 Hom.: 36

Bravo AF: 0.0261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0783 AC: 345

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00784 AC: 952

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.79	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.047
Sift	Benign	0.24	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0090	B;B
Vest4		0.056
MVP		0.35
MPC		0.32
ClinPred		0.029	T
GERP RS		1.7
Varity_R		0.12
gMVP		0.45

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: rs61737287; hg19: chr8-27729527;