10-104124358-C-T

Position:

• chr10-104124358-C-T

Variant summary

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

The NM_001002759.2(SFR1):​c.546+234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,860 control chromosomes in the GnomAD database, including 11,771 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 0.35 (11771 hom., cov: 32)
• Consequence: SFR1 NM_001002759.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFR1	NM_001002759.2	c.546+234C>T		intron_variant		ENST00000369727.4	NP_001002759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFR1	ENST00000369727.4	c.546+234C>T		intron_variant		2	NM_001002759.2	ENSP00000358742.3
SFR1	ENST00000369729.7	c.507+234C>T		intron_variant		1		ENSP00000358744.3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53371 AN: 151742 Hom.: 11777 Cov.: 32

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.351 AC: 53351 AN: 151860 Hom.: 11771 Cov.: 32 AF XY: 0.354 AC XY: 26286 AN XY: 74228

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.350

Alfa AF: 0.404 Hom.: 4270

Bravo AF: 0.323

Asia WGS AF: 0.291 AC: 1009 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.57

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: rs10883969; hg19: chr10-105884116;