rs9620047

chr22-42429033-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAM1	NM_145912.8	c.121+3204T>C		intron_variant		ENST00000329021.10
NFAM1	NM_001318323.3	c.121+3204T>C		intron_variant
NFAM1	NM_001371362.1	c.-36+7923T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10	c.121+3204T>C		intron_variant		1	NM_145912.8	P1
NFAM1	ENST00000355469.4	n.126+3204T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.0854

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.188

Alfa AF: 0.152 Hom.: 2574

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

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: rs9620047; hg19: chr22-42825039;