chr22-42383012-T-C

Position:

• chr22-42383012-T-C

Variant summary

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

The NM_145912.8(NFAM1):​c.*2149A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,676 control chromosomes in the GnomAD database, including 8,174 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 0.32 (8115 hom., cov: 32)
  • Exomes 𝑓: 0.34 (59 hom.)
• Consequence: NFAM1 NM_145912.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAM1	NM_145912.8	c.*2149A>G		3_prime_UTR_variant	6/6	ENST00000329021.10
NFAM1	NM_001318323.3	c.*2252A>G		3_prime_UTR_variant	5/5
NFAM1	NM_001371362.1	c.*2149A>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10	c.*2149A>G		3_prime_UTR_variant	6/6	1	NM_145912.8	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48168 AN: 151620 Hom.: 8103 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.339 AC: 318 AN: 938 Hom.: 59 Cov.: 0 AF XY: 0.351 AC XY: 252 AN XY: 718

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.318 AC: 48201 AN: 151738 Hom.: 8115 Cov.: 32 AF XY: 0.319 AC XY: 23661 AN XY: 74154

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.328

Alfa AF: 0.323 Hom.: 1781

Bravo AF: 0.324

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.44

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: rs1057157; hg19: chr22-42779018;