rs10786783

chr10-104123007-A-G

Variant summary

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

The NM_001002759.2(SFR1):c.56A>G(p.Asp19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,054 control chromosomes in the GnomAD database, including 25,593 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (4013 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21580 hom.)
• Consequence: SFR1 NM_001002759.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

Genes affected

SFR1 (HGNC:29574): (SWI5 dependent homologous recombination repair protein 1) Enables nuclear receptor coactivator activity. Involved in cellular response to estrogen stimulus; double-strand break repair via homologous recombination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of Swi5-Sfr1 complex. [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=0.0039505363).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFR1	NM_001002759.2	c.56A>G	p.Asp19Gly	missense_variant	2/4	ENST00000369727.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFR1	ENST00000369727.4	c.56A>G	p.Asp19Gly	missense_variant	2/4	2	NM_001002759.2	A1
SFR1	ENST00000369729.7	c.17A>G	p.Asp6Gly	missense_variant	2/4	1		P4
SFR1	ENST00000463224.5	n.140A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32325 AN: 151960 Hom.: 4002 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.168 AC: 42226 AN: 251156 Hom.: 4065 AF XY: 0.167 AC XY: 22628 AN XY: 135780

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.167 AC: 243460 AN: 1460974 Hom.: 21580 Cov.: 32 AF XY: 0.166 AC XY: 120814 AN XY: 726816

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.213 AC: 32359 AN: 152080 Hom.: 4013 Cov.: 32 AF XY: 0.211 AC XY: 15657 AN XY: 74340

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.200

Alfa AF: 0.164 Hom.: 3128

Bravo AF: 0.220

TwinsUK AF: 0.174 AC: 644

ALSPAC AF: 0.164 AC: 631

ESP6500AA AF: 0.341 AC: 1503

ESP6500EA AF: 0.159 AC: 1365

ExAC AF: 0.174 AC: 21078

Asia WGS AF: 0.239 AC: 830 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	14
Dann	Benign	0.96
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.060
Sift	Benign	0.23	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.19	.;B
Vest4		0.13
MPC		0.019
ClinPred		0.026	T
GERP RS		0.86
Varity_R		0.098
gMVP		0.052

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10786783; hg19: chr10-105882765; COSMIC: COSV60479996;