22-42425495-A-G

Position:

• chr22-42425495-A-G

Variant summary

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

The ENST00000329021.10(NFAM1):​c.121+6742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,832 control chromosomes in the GnomAD database, including 24,573 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 0.53 (24573 hom., cov: 31)
• Consequence: NFAM1 ENST00000329021.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.121+6742T>C		intron_variant		ENST00000329021.10	NP_666017.1
NFAM1	NM_001318323.3	c.121+6742T>C		intron_variant			NP_001305252.1
NFAM1	NM_001371362.1	c.-36+11461T>C		intron_variant			NP_001358291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.121+6742T>C		intron_variant		1	NM_145912.8	ENSP00000333680	P1
NFAM1	ENST00000355469.4	n.126+6742T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80261 AN: 151714 Hom.: 24510 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.529 AC: 80384 AN: 151832 Hom.: 24573 Cov.: 31 AF XY: 0.522 AC XY: 38720 AN XY: 74196

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.478

Alfa AF: 0.467 Hom.: 2156

Bravo AF: 0.542

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.33

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: rs8141826; hg19: chr22-42821501;