NM_001130012.3:c.793-79G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001130012.3(NHERF2):​c.793-79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,239,248 control chromosomes in the GnomAD database, including 25,195 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 0.25 (5786 hom., cov: 32)
  • Exomes 𝑓: 0.18 (19409 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	NM_001130012.3	MANE Select	c.793-79G>T		intron	N/A	NP_001123484.1
	NHERF2	NM_004785.6		c.793-79G>T		intron	N/A	NP_004776.3
	NHERF2	NM_001252073.2		c.460-79G>T		intron	N/A	NP_001239002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.793-79G>T		intron	N/A	ENSP00000408005.2
	NHERF2	ENST00000432365.6	TSL:1	c.793-79G>T		intron	N/A	ENSP00000402857.2
	NHERF2	ENST00000563587.5	TSL:2	c.475-79G>T		intron	N/A	ENSP00000455909.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37964 AN: 151854 Hom.: 5780 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.176 AC: 191557 AN: 1087276 Hom.: 19409 AF XY: 0.172 AC XY: 94872 AN XY: 550352

African (AFR) AF: 0.405 AC: 9935 AN: 24530

American (AMR) AF: 0.132 AC: 4701 AN: 35498

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 5824 AN: 23066

East Asian (EAS) AF: 0.000491 AC: 17 AN: 34622

South Asian (SAS) AF: 0.101 AC: 7432 AN: 73370

European-Finnish (FIN) AF: 0.245 AC: 11930 AN: 48716

Middle Eastern (MID) AF: 0.253 AC: 1262 AN: 4994

European-Non Finnish (NFE) AF: 0.178 AC: 141579 AN: 794766

Other (OTH) AF: 0.186 AC: 8877 AN: 47714

GnomAD4 genome AF: 0.250 AC: 37993 AN: 151972 Hom.: 5786 Cov.: 32 AF XY: 0.246 AC XY: 18266 AN XY: 74294

African (AFR) AF: 0.422 AC: 17489 AN: 41398

American (AMR) AF: 0.180 AC: 2752 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3464

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0983 AC: 474 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2694 AN: 10580

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13014 AN: 67942

Other (OTH) AF: 0.230 AC: 483 AN: 2104

Alfa AF: 0.110 Hom.: 180

Bravo AF: 0.252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.72
PhyloP100		-1.8
Mutation Taster		=12/88	disease causing (long InDel)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -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; COSMIC: COSV54594353; COSMIC: COSV54594353;