chr22-42419750-C-G

Position:

• chr22-42419750-C-G

Variant summary

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

The NM_145912.8(NFAM1):​c.122-8014G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,134 control chromosomes in the GnomAD database, including 4,385 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 0.23 (4385 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

NFAM1 (HGNC:):

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 = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.122-8014G>C		intron_variant		ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1	c.-35-8014G>C		intron_variant			NP_001358291.1
NFAM1	NM_001318323.3	c.122-8014G>C		intron_variant			NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.122-8014G>C		intron_variant		1	NM_145912.8	ENSP00000333680.5
NFAM1	ENST00000355469.4	n.127-8014G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34638 AN: 152016 Hom.: 4377 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.228 AC: 34657 AN: 152134 Hom.: 4385 Cov.: 32 AF XY: 0.228 AC XY: 16954 AN XY: 74376

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.248

Alfa AF: 0.229 Hom.: 550

Bravo AF: 0.237

Asia WGS AF: 0.208 AC: 722 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	0.71
DANN	Benign	0.65

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: rs4822127; hg19: chr22-42815756;