rs2205849

Variant names:

• chr1-169712216-T-C
• rs2205849
• ENST00000498289.5:n.851+28284T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000498289.5(FIRRM):​n.851+28284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,064 control chromosomes in the GnomAD database, including 2,955 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 0.19 (2955 hom., cov: 32)
• Consequence: FIRRM ENST00000498289.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 9 publications found

Genes affected

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

SELL (HGNC:10720): (selectin L) This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498289.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIRRM	ENST00000498289.5	TSL:2	n.851+28284T>C		intron	N/A
	SELL	ENST00000878074.1		c.-466A>G		upstream_gene	N/A	ENSP00000548133.1
	SELL	ENST00000878075.1		c.-450A>G		upstream_gene	N/A	ENSP00000548134.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28544 AN: 151944 Hom.: 2946 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.188 AC: 28592 AN: 152064 Hom.: 2955 Cov.: 32 AF XY: 0.190 AC XY: 14153 AN XY: 74326

African (AFR) AF: 0.243 AC: 10091 AN: 41488

American (AMR) AF: 0.246 AC: 3753 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5174

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4812

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10580

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9231 AN: 68000

Other (OTH) AF: 0.208 AC: 438 AN: 2110

Alfa AF: 0.172 Hom.: 823

Bravo AF: 0.200

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs2205849; hg19: chr1-169681357;