chr22-42405446-A-G

Variant names:

• chr22-42405446-A-G
• rs2142831
• NM_145912.8:c.564+3989T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.564+3989T>C		intron_variant	Intron 3 of 5	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1	c.408+3989T>C		intron_variant	Intron 5 of 7		NP_001358291.1
NFAM1	NM_001318323.3	c.451+5961T>C		intron_variant	Intron 2 of 4		NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.564+3989T>C		intron_variant	Intron 3 of 5	1	NM_145912.8	ENSP00000333680.5

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

African (AFR) AF: 0.769 AC: 31927 AN: 41500

American (AMR) AF: 0.498 AC: 7607 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1684 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2403 AN: 5144

South Asian (SAS) AF: 0.605 AC: 2918 AN: 4822

European-Finnish (FIN) AF: 0.274 AC: 2902 AN: 10574

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25271 AN: 67936

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.446 Hom.: 31021

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
PhyloP100		-0.19
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: rs2142831; hg19: chr22-42801452;