rs9620047

Variant names:

• chr22-42429033-A-G
• rs9620047
• NM_145912.8:c.121+3204T>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.121+3204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,108 control chromosomes in the GnomAD database, including 3,620 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 0.19 (3620 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.121+3204T>C		intron_variant	Intron 1 of 5	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1	c.-36+7923T>C		intron_variant	Intron 3 of 7		NP_001358291.1
NFAM1	NM_001318323.3	c.121+3204T>C		intron_variant	Intron 1 of 4		NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.121+3204T>C		intron_variant	Intron 1 of 5	1	NM_145912.8	ENSP00000333680.5
NFAM1	ENST00000355469.4	n.126+3204T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29382 AN: 151990 Hom.: 3603 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0854

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.194 AC: 29435 AN: 152108 Hom.: 3620 Cov.: 32 AF XY: 0.191 AC XY: 14178 AN XY: 74344

African (AFR) AF: 0.335 AC: 13894 AN: 41472

American (AMR) AF: 0.128 AC: 1965 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3470

East Asian (EAS) AF: 0.153 AC: 792 AN: 5160

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4818

European-Finnish (FIN) AF: 0.0854 AC: 905 AN: 10602

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8892 AN: 67976

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.153 Hom.: 3132

Bravo AF: 0.197

Asia WGS AF: 0.273 AC: 947 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	0.69
DANN	Benign	0.67
PhyloP100		-0.71
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: rs9620047; hg19: chr22-42825039;