rs735537

Variant names:

• chr22-42416465-A-G
• rs735537
• NM_145912.8:c.122-4729T>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.122-4729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,908 control chromosomes in the GnomAD database, including 25,998 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 0.56 (25998 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.122-4729T>C		intron_variant	Intron 1 of 5	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1	c.-35-4729T>C		intron_variant	Intron 3 of 7		NP_001358291.1
NFAM1	NM_001318323.3	c.122-4729T>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.122-4729T>C		intron_variant	Intron 1 of 5	1	NM_145912.8	ENSP00000333680.5
NFAM1	ENST00000355469.4	n.127-4729T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85290 AN: 151790 Hom.: 25939 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.562 AC: 85411 AN: 151908 Hom.: 25998 Cov.: 32 AF XY: 0.555 AC XY: 41231 AN XY: 74232

African (AFR) AF: 0.808 AC: 33431 AN: 41386

American (AMR) AF: 0.548 AC: 8365 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2399 AN: 5148

South Asian (SAS) AF: 0.632 AC: 3041 AN: 4812

European-Finnish (FIN) AF: 0.342 AC: 3617 AN: 10578

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30950 AN: 67940

Other (OTH) AF: 0.539 AC: 1137 AN: 2110

Alfa AF: 0.488 Hom.: 3695

Bravo AF: 0.585

Asia WGS AF: 0.594 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.53
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: rs735537; hg19: chr22-42812471;