rs13055337

Positions:

• chr22-42389054-C-G
• chr22-42389054-C-T

Variant summary

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

The NM_145912.8(NFAM1):​c.664-1976G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,148 control chromosomes in the GnomAD database, including 3,739 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 0.21 (3739 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.664-1976G>C		intron_variant		ENST00000329021.10	NP_666017.1
NFAM1	NM_001318323.3	c.551-1976G>C		intron_variant			NP_001305252.1
NFAM1	NM_001371362.1	c.508-1976G>C		intron_variant			NP_001358291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.664-1976G>C		intron_variant		1	NM_145912.8	ENSP00000333680	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31258 AN: 152030 Hom.: 3729 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0909

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.206 AC: 31309 AN: 152148 Hom.: 3739 Cov.: 32 AF XY: 0.204 AC XY: 15198 AN XY: 74388

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0909

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.179

Alfa AF: 0.0779 Hom.: 101

Bravo AF: 0.211

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
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: rs13055337; hg19: chr22-42785060;