rs3211995

Variant names:

• chr16-2039005-G-A
• rs3211995
• NM_001130012.3:c.*1021G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2039005-G-A
• chr16-2039005-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130012.3(NHERF2):​c.*1021G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,398 control chromosomes in the GnomAD database, including 6,219 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 (6217 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: NHERF2 NM_001130012.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	NM_001130012.3	MANE Select	c.*1021G>A		3_prime_UTR	Exon 7 of 7	NP_001123484.1	Q15599-1
	NHERF2	NM_004785.6		c.*1021G>A		3_prime_UTR	Exon 7 of 7	NP_004776.3	Q15599-2
	NHERF2	NM_001252073.2		c.*1021G>A		3_prime_UTR	Exon 6 of 6	NP_001239002.1	Q15599-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.*1021G>A		3_prime_UTR	Exon 7 of 7	ENSP00000408005.2	Q15599-1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37390 AN: 152092 Hom.: 6204 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.128 AC: 24 AN: 188 Hom.: 2 Cov.: 0 AF XY: 0.115 AC XY: 14 AN XY: 122

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.164 AC: 22 AN: 134

Other (OTH) AF: 0.00 AC: 0 AN: 18

GnomAD4 genome AF: 0.246 AC: 37441 AN: 152210 Hom.: 6217 Cov.: 33 AF XY: 0.242 AC XY: 18024 AN XY: 74426

African (AFR) AF: 0.474 AC: 19669 AN: 41532

American (AMR) AF: 0.176 AC: 2691 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0904 AC: 437 AN: 4832

European-Finnish (FIN) AF: 0.211 AC: 2244 AN: 10612

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10932 AN: 67982

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.200 Hom.: 4860

Bravo AF: 0.253

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.42
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: rs3211995; hg19: chr16-2089006;