rs4822129

Variant names:

• chr22-42427910-G-A
• rs4822129
• NM_145912.8:c.121+4327C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145912.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAM1	NM_145912.8	MANE Select	c.121+4327C>T		intron	N/A	NP_666017.1
	NFAM1	NM_001371362.1		c.-36+9046C>T		intron	N/A	NP_001358291.1
	NFAM1	NM_001318323.3		c.121+4327C>T		intron	N/A	NP_001305252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAM1	ENST00000329021.10	TSL:1 MANE Select	c.121+4327C>T		intron	N/A	ENSP00000333680.5
	NFAM1	ENST00000355469.4	TSL:3	n.126+4327C>T		intron	N/A

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

African (AFR) AF: 0.0466 AC: 1935 AN: 41564

American (AMR) AF: 0.319 AC: 4871 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.174 AC: 902 AN: 5182

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13296 AN: 67974

Other (OTH) AF: 0.182 AC: 384 AN: 2114

Alfa AF: 0.183 Hom.: 5754

Bravo AF: 0.172

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.44
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4822129; hg19: chr22-42823916;