rs10786783

Variant names:

• chr10-104123007-A-G
• rs10786783
• NM_001002759.2:c.56A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.21 (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
• Publications: 22 publications found

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]

ENSG00000294028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002759.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFR1	NM_001002759.2	MANE Select	c.56A>G	p.Asp19Gly	missense	Exon 2 of 4	NP_001002759.1
	SFR1	NM_001384829.1		c.17A>G	p.Asp6Gly	missense	Exon 2 of 4	NP_001371758.1
	SFR1	NM_001384830.1		c.17A>G	p.Asp6Gly	missense	Exon 2 of 4	NP_001371759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFR1	ENST00000369727.4	TSL:2 MANE Select	c.56A>G	p.Asp19Gly	missense	Exon 2 of 4	ENSP00000358742.3
	SFR1	ENST00000369729.7	TSL:1	c.17A>G	p.Asp6Gly	missense	Exon 2 of 4	ENSP00000358744.3
	SFR1	ENST00000463224.5	TSL:3	n.140A>G		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.168 AC: 42226 AN: 251156 AF XY: 0.167

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 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

African (AFR) AF: 0.355 AC: 11863 AN: 33420

American (AMR) AF: 0.107 AC: 4798 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3069 AN: 26124

East Asian (EAS) AF: 0.219 AC: 8681 AN: 39682

South Asian (SAS) AF: 0.171 AC: 14777 AN: 86172

European-Finnish (FIN) AF: 0.158 AC: 8433 AN: 53364

Middle Eastern (MID) AF: 0.177 AC: 1015 AN: 5748

European-Non Finnish (NFE) AF: 0.162 AC: 180162 AN: 1111392

Other (OTH) AF: 0.177 AC: 10662 AN: 60354

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

African (AFR) AF: 0.346 AC: 14337 AN: 41426

American (AMR) AF: 0.158 AC: 2413 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1197 AN: 5180

South Asian (SAS) AF: 0.164 AC: 790 AN: 4828

European-Finnish (FIN) AF: 0.150 AC: 1584 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10831 AN: 67986

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.176 Hom.: 5364

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 v4.9

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
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.44
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.060
Sift	Benign	0.23	T
Sift4G	Benign	0.21	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10786783; hg19: chr10-105882765; COSMIC: COSV60479996;