rs1856746

Variant names:

• chr1-206970077-A-G
• rs1856746
• NM_001170631.2:c.39+10T>C

Variant summary

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

The NM_001170631.2(FCAMR):​c.39+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,194 control chromosomes in the GnomAD database, including 186,225 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 0.57 (27048 hom., cov: 31)
  • Exomes 𝑓: 0.46 (159177 hom.)
• Consequence: FCAMR NM_001170631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 27 publications found

Genes affected

FCAMR (HGNC:24692): (Fc alpha and mu receptor) Predicted to enable IgA binding activity; IgM binding activity; and transmembrane signaling receptor activity. Predicted to be involved in adaptive immune response. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170631.2. 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
	FCAMR	NM_001170631.2	MANE Select	c.39+10T>C		intron	N/A	NP_001164102.1	Q8WWV6-6
	FCAMR	NM_001122979.3		c.39+10T>C		intron	N/A	NP_001116451.1	A0AB56DZ37
	FCAMR	NM_032029.5		c.39+10T>C		intron	N/A	NP_114418.2	A0AB56DZ37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAMR	ENST00000324852.9	TSL:2 MANE Select	c.39+10T>C		intron	N/A	ENSP00000316491.4	Q8WWV6-6
	FCAMR	ENST00000450945.3	TSL:1	c.39+10T>C		intron	N/A	ENSP00000392707.2	A0AB56DZ37
	FCAMR	ENST00000400962.8	TSL:5	c.39+10T>C		intron	N/A	ENSP00000383746.3	A0AB56DZ37

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86227 AN: 151900 Hom.: 26984 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.471 AC: 117049 AN: 248744 AF XY: 0.457

Gnomad AFR exome AF: 0.866

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.433

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.459 AC: 671024 AN: 1461178 Hom.: 159177 Cov.: 39 AF XY: 0.454 AC XY: 330023 AN XY: 726946

African (AFR) AF: 0.873 AC: 29207 AN: 33450

American (AMR) AF: 0.510 AC: 22811 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 14678 AN: 26118

East Asian (EAS) AF: 0.429 AC: 16999 AN: 39664

South Asian (SAS) AF: 0.297 AC: 25581 AN: 86232

European-Finnish (FIN) AF: 0.396 AC: 21163 AN: 53406

Middle Eastern (MID) AF: 0.564 AC: 3255 AN: 5768

European-Non Finnish (NFE) AF: 0.457 AC: 507941 AN: 1111502

Other (OTH) AF: 0.487 AC: 29389 AN: 60354

GnomAD4 genome AF: 0.568 AC: 86350 AN: 152016 Hom.: 27048 Cov.: 31 AF XY: 0.558 AC XY: 41467 AN XY: 74298

African (AFR) AF: 0.855 AC: 35472 AN: 41498

American (AMR) AF: 0.525 AC: 8021 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3466

East Asian (EAS) AF: 0.447 AC: 2302 AN: 5148

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4820

European-Finnish (FIN) AF: 0.381 AC: 4028 AN: 10574

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31436 AN: 67914

Other (OTH) AF: 0.584 AC: 1231 AN: 2108

Alfa AF: 0.505 Hom.: 37304

Bravo AF: 0.593

Asia WGS AF: 0.395 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		-1.4
PromoterAI		0.052	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1856746; hg19: chr1-207143422; COSMIC: COSV61367093;