1-207701830-G-T

Variant names:

• chr1-207701830-G-T
• rs4844614
• NM_175710.2:c.1328+212G>T

Variant summary

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

The NM_175710.2(CR1L):​c.1328+212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 763,328 control chromosomes in the GnomAD database, including 32,538 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 0.28 (6450 hom., cov: 31)
  • Exomes 𝑓: 0.28 (26088 hom.)
• Consequence: CR1L NM_175710.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 27 publications found

Genes affected

CR1L (HGNC:2335): (complement C3b/C4b receptor 1 like) Acts upstream of or within regulation of complement activation and regulation of complement-dependent cytotoxicity. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308069 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1L	NM_175710.2	c.1328+212G>T		intron_variant	Intron 9 of 11	ENST00000508064.7	NP_783641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1L	ENST00000508064.7	c.1328+212G>T		intron_variant	Intron 9 of 11	1	NM_175710.2	ENSP00000421736.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43015 AN: 151848 Hom.: 6434 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.283 AC: 173034 AN: 611362 Hom.: 26088 AF XY: 0.284 AC XY: 92654 AN XY: 326568

African (AFR) AF: 0.268 AC: 4401 AN: 16422

American (AMR) AF: 0.474 AC: 16156 AN: 34100

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 4009 AN: 19750

East Asian (EAS) AF: 0.359 AC: 11119 AN: 30972

South Asian (SAS) AF: 0.335 AC: 21131 AN: 63040

European-Finnish (FIN) AF: 0.317 AC: 14693 AN: 46282

Middle Eastern (MID) AF: 0.214 AC: 781 AN: 3654

European-Non Finnish (NFE) AF: 0.252 AC: 92264 AN: 365564

Other (OTH) AF: 0.269 AC: 8480 AN: 31578

GnomAD4 genome AF: 0.283 AC: 43059 AN: 151966 Hom.: 6450 Cov.: 31 AF XY: 0.292 AC XY: 21684 AN XY: 74254

African (AFR) AF: 0.265 AC: 10995 AN: 41460

American (AMR) AF: 0.431 AC: 6560 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3464

East Asian (EAS) AF: 0.327 AC: 1685 AN: 5158

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3345 AN: 10542

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17158 AN: 67970

Other (OTH) AF: 0.292 AC: 617 AN: 2114

Alfa AF: 0.263 Hom.: 20345

Bravo AF: 0.292

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4844614; hg19: chr1-207875175; COSMIC: COSV54329836;