rs12447809

Variant names:

• chr16-2037459-G-C
• rs12447809
• NM_001130012.3:c.793-79G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2037459-G-C
• chr16-2037459-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130012.3(NHERF2):​c.793-79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 10 publications found

Genes affected

NHERF2 (HGNC:11076): (NHERF family PDZ scaffold protein 2) This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHERF2	NM_001130012.3	c.793-79G>C		intron_variant	Intron 5 of 6	ENST00000424542.7	NP_001123484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7	c.793-79G>C		intron_variant	Intron 5 of 6	1	NM_001130012.3	ENSP00000408005.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089558 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 551462

African (AFR) AF: 0.00 AC: 0 AN: 24590

American (AMR) AF: 0.00 AC: 0 AN: 35512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23102

East Asian (EAS) AF: 0.00 AC: 0 AN: 34622

South Asian (SAS) AF: 0.00 AC: 0 AN: 73412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5008

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 796770

Other (OTH) AF: 0.0000209 AC: 1 AN: 47780

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.60
PhyloP100		-1.8

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: rs12447809; hg19: chr16-2087460;