11-67497208-C-T

Variant names:

• chr11-67497208-C-T
• rs2276120
• NM_004910.3:c.2146+23G>A

Variant summary

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

The NM_004910.3(PITPNM1):​c.2146+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,555,864 control chromosomes in the GnomAD database, including 121,786 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 0.34 (9334 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112452 hom.)
• Consequence: PITPNM1 NM_004910.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 13 publications found

Genes affected

PITPNM1 (HGNC:9003): (phosphatidylinositol transfer protein membrane associated 1) PITPNM1 belongs to a family of membrane-associated phosphatidylinositol transfer domain-containing proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein (Ocaka et al., 2005 [PubMed 15627748]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM1	NM_004910.3	c.2146+23G>A		intron_variant	Intron 14 of 23	ENST00000356404.8	NP_004901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM1	ENST00000356404.8	c.2146+23G>A		intron_variant	Intron 14 of 23	1	NM_004910.3	ENSP00000348772.3
PITPNM1	ENST00000534749.5	c.2146+23G>A		intron_variant	Intron 13 of 22	1		ENSP00000437286.1
PITPNM1	ENST00000436757.7	c.2146+23G>A		intron_variant	Intron 14 of 23	1		ENSP00000398787.2
PITPNM1	ENST00000527370.5	n.1000G>A		non_coding_transcript_exon_variant	Exon 4 of 13	2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51362 AN: 151976 Hom.: 9335 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.329

GnomAD2 exomes AF: 0.368 AC: 77956 AN: 211836 AF XY: 0.364

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.533

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.174

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.394 AC: 552703 AN: 1403772 Hom.: 112452 Cov.: 29 AF XY: 0.391 AC XY: 270436 AN XY: 692502

African (AFR) AF: 0.220 AC: 6953 AN: 31554

American (AMR) AF: 0.518 AC: 19487 AN: 37632

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 7263 AN: 23498

East Asian (EAS) AF: 0.159 AC: 6134 AN: 38524

South Asian (SAS) AF: 0.289 AC: 23280 AN: 80440

European-Finnish (FIN) AF: 0.330 AC: 16764 AN: 50762

Middle Eastern (MID) AF: 0.391 AC: 1745 AN: 4460

European-Non Finnish (NFE) AF: 0.417 AC: 449559 AN: 1079228

Other (OTH) AF: 0.373 AC: 21518 AN: 57674

GnomAD4 genome AF: 0.338 AC: 51364 AN: 152092 Hom.: 9334 Cov.: 32 AF XY: 0.332 AC XY: 24674 AN XY: 74342

African (AFR) AF: 0.220 AC: 9120 AN: 41490

American (AMR) AF: 0.415 AC: 6337 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1066 AN: 3468

East Asian (EAS) AF: 0.175 AC: 905 AN: 5174

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4826

European-Finnish (FIN) AF: 0.326 AC: 3449 AN: 10578

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27997 AN: 67960

Other (OTH) AF: 0.325 AC: 685 AN: 2106

Alfa AF: 0.360 Hom.: 2923

Bravo AF: 0.344

Asia WGS AF: 0.260 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.85
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2276120; hg19: chr11-67264679; COSMIC: COSV62707260; COSMIC: COSV62707260;