rs4656704

Variant names:

• chr1-169719087-A-G
• rs4656704
• ENST00000498289.5:n.851+35155A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498289.5(FIRRM):​n.851+35155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,828 control chromosomes in the GnomAD database, including 6,847 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 0.30 (6847 hom., cov: 31)
• Consequence: FIRRM ENST00000498289.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 5 publications found

Genes affected

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIRRM	ENST00000498289.5	n.851+35155A>G		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44907 AN: 151710 Hom.: 6823 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.296 AC: 44983 AN: 151828 Hom.: 6847 Cov.: 31 AF XY: 0.299 AC XY: 22165 AN XY: 74188

African (AFR) AF: 0.337 AC: 13959 AN: 41386

American (AMR) AF: 0.326 AC: 4971 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1703 AN: 5142

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2836 AN: 10542

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17311 AN: 67924

Other (OTH) AF: 0.321 AC: 677 AN: 2106

Alfa AF: 0.284 Hom.: 1008

Bravo AF: 0.302

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.47
DANN	Benign	0.29
PhyloP100		-0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4656704; hg19: chr1-169688228;