rs4656699

Variant names:

• chr1-169718418-C-T
• rs4656699
• ENST00000498289.5:n.851+34486C>T

Variant summary

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

The ENST00000498289.5(FIRRM):​n.851+34486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,156 control chromosomes in the GnomAD database, including 1,089 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 0.11 (1089 hom., cov: 32)
• Consequence: FIRRM ENST00000498289.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 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+34486C>T		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16572 AN: 152036 Hom.: 1085 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.109 AC: 16592 AN: 152156 Hom.: 1089 Cov.: 32 AF XY: 0.111 AC XY: 8278 AN XY: 74390

African (AFR) AF: 0.0763 AC: 3170 AN: 41534

American (AMR) AF: 0.198 AC: 3029 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5176

South Asian (SAS) AF: 0.141 AC: 678 AN: 4818

European-Finnish (FIN) AF: 0.136 AC: 1446 AN: 10600

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6506 AN: 67970

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.101 Hom.: 121

Bravo AF: 0.115

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.28
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs4656699; hg19: chr1-169687559;