rs12160838

Variant names:

• chr22-42397557-G-A
• rs12160838
• NM_145912.8:c.663+301C>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.663+301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,998 control chromosomes in the GnomAD database, including 2,265 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 (2265 hom., cov: 32)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFAM1	NM_145912.8	c.663+301C>T		intron_variant	Intron 4 of 5	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1	c.507+301C>T		intron_variant	Intron 6 of 7		NP_001358291.1
NFAM1	NM_001318323.3	c.550+301C>T		intron_variant	Intron 3 of 4		NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10	c.663+301C>T		intron_variant	Intron 4 of 5	1	NM_145912.8	ENSP00000333680.5

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25312 AN: 151880 Hom.: 2264 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0932

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.167 AC: 25329 AN: 151998 Hom.: 2265 Cov.: 32 AF XY: 0.165 AC XY: 12271 AN XY: 74284

African (AFR) AF: 0.212 AC: 8777 AN: 41462

American (AMR) AF: 0.167 AC: 2546 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 323 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5170

South Asian (SAS) AF: 0.0899 AC: 433 AN: 4818

European-Finnish (FIN) AF: 0.191 AC: 2019 AN: 10546

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10637 AN: 67944

Other (OTH) AF: 0.156 AC: 330 AN: 2116

Alfa AF: 0.162 Hom.: 3482

Bravo AF: 0.171

Asia WGS AF: 0.0540 AC: 189 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	0.090
DANN	Benign	0.47
PhyloP100		-2.0
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: rs12160838; hg19: chr22-42793563;