12-65055291-A-G

Variant names:

• chr12-65055291-A-G
• rs1026025
• NM_007191.5:c.923-78T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007191.5(WIF1):​c.923-78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,467,238 control chromosomes in the GnomAD database, including 43,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3299 hom., cov: 33)
  • Exomes 𝑓: 0.24 (40333 hom.)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.300
• Publications: 3 publications found

Genes affected

WIF1 (HGNC:18081): (WNT inhibitory factor 1) The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-65055291-A-G is Benign according to our data. Variant chr12-65055291-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007191.5. 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
	WIF1	NM_007191.5	MANE Select	c.923-78T>C		intron	N/A	NP_009122.2	Q9Y5W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	ENST00000286574.9	TSL:1 MANE Select	c.923-78T>C		intron	N/A	ENSP00000286574.4	Q9Y5W5
	WIF1	ENST00000954483.1		c.893-78T>C		intron	N/A	ENSP00000624542.1
	WIF1	ENST00000954485.1		c.893-78T>C		intron	N/A	ENSP00000624544.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30165 AN: 152008 Hom.: 3298 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.240 AC: 315827 AN: 1315112 Hom.: 40333 AF XY: 0.238 AC XY: 155078 AN XY: 651696

African (AFR) AF: 0.113 AC: 3301 AN: 29140

American (AMR) AF: 0.280 AC: 7921 AN: 28246

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 3817 AN: 22112

East Asian (EAS) AF: 0.000850 AC: 32 AN: 37662

South Asian (SAS) AF: 0.144 AC: 10172 AN: 70670

European-Finnish (FIN) AF: 0.235 AC: 11556 AN: 49182

Middle Eastern (MID) AF: 0.114 AC: 604 AN: 5318

European-Non Finnish (NFE) AF: 0.262 AC: 266877 AN: 1018208

Other (OTH) AF: 0.212 AC: 11547 AN: 54574

GnomAD4 genome AF: 0.198 AC: 30170 AN: 152126 Hom.: 3299 Cov.: 33 AF XY: 0.194 AC XY: 14392 AN XY: 74376

African (AFR) AF: 0.118 AC: 4894 AN: 41510

American (AMR) AF: 0.251 AC: 3831 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5180

South Asian (SAS) AF: 0.126 AC: 608 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2368 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17145 AN: 67970

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.214 Hom.: 480

Bravo AF: 0.198

Asia WGS AF: 0.0640 AC: 226 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.30
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: rs1026025; hg19: chr12-65449071;