22-42427910-G-A

Position:

• chr22-42427910-G-A

Variant summary

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

The NM_145912.8(NFAM1):​c.121+4327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,200 control chromosomes in the GnomAD database, including 2,790 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 0.17 (2790 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAM1	NM_145912.8	c.121+4327C>T		intron_variant		ENST00000329021.10
NFAM1	NM_001318323.3	c.121+4327C>T		intron_variant
NFAM1	NM_001371362.1	c.-36+9046C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10	c.121+4327C>T		intron_variant		1	NM_145912.8	P1
NFAM1	ENST00000355469.4	n.126+4327C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25601 AN: 152082 Hom.: 2782 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.168 AC: 25617 AN: 152200 Hom.: 2790 Cov.: 32 AF XY: 0.173 AC XY: 12851 AN XY: 74422

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.182

Alfa AF: 0.193 Hom.: 4098

Bravo AF: 0.172

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
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: rs4822129; hg19: chr22-42823916;