rs2142831

chr22-42405446-A-Gchr22-42405446-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145912.8(NFAM1):c.564+3989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,018 control chromosomes in the GnomAD database, including 21,549 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 0.50 (21549 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

Genes affected

NFAM1 (HGNC:29872): (NFAT activating protein with ITAM motif 1) The protein encoded by this gene is a type I membrane receptor that activates cytokine gene promoters such as the IL-13 and TNF-alpha promoters. The encoded protein contains an immunoreceptor tyrosine-based activation motif (ITAM) and is thought to regulate the signaling and development of B-cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAM1	NM_145912.8	c.564+3989T>C		intron_variant		ENST00000329021.10
NFAM1	NM_001318323.3	c.451+5961T>C		intron_variant
NFAM1	NM_001371362.1	c.408+3989T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10	c.564+3989T>C		intron_variant		1	NM_145912.8	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76076 AN: 151900 Hom.: 21489 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.501 AC: 76196 AN: 152018 Hom.: 21549 Cov.: 32 AF XY: 0.497 AC XY: 36904 AN XY: 74314

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.481

Alfa AF: 0.409 Hom.: 17059

Bravo AF: 0.525

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.8
Dann	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs2142831; hg19: chr22-42801452;