22-42421646-T-G

Variant names:

• chr22-42421646-T-G
• rs9623589
• NM_145912.8:c.122-9910A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145912.8(NFAM1):​c.122-9910A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,786 control chromosomes in the GnomAD database, including 8,075 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 0.32 (8075 hom., cov: 31)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 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.122-9910A>C		intron	N/A	NP_666017.1
	NFAM1	NM_001371362.1		c.-35-9910A>C		intron	N/A	NP_001358291.1
	NFAM1	NM_001318323.3		c.122-9910A>C		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.122-9910A>C		intron	N/A	ENSP00000333680.5
	NFAM1	ENST00000355469.4	TSL:3	n.127-9910A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48604 AN: 151668 Hom.: 8050 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.321 AC: 48689 AN: 151786 Hom.: 8075 Cov.: 31 AF XY: 0.319 AC XY: 23623 AN XY: 74146

African (AFR) AF: 0.344 AC: 14234 AN: 41318

American (AMR) AF: 0.433 AC: 6600 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1374 AN: 5150

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4818

European-Finnish (FIN) AF: 0.245 AC: 2582 AN: 10550

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20488 AN: 67942

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.284 Hom.: 2585

Bravo AF: 0.336

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.028
DANN	Benign	0.51
PhyloP100		-0.45
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: rs9623589; hg19: chr22-42817652;