chr16-48198625-A-G

Variant names:

• chr16-48198625-A-G
• rs7203695
• NM_001370497.1:c.2083-350T>C

Variant summary

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

The NM_001370497.1(ABCC11):​c.2083-350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,814 control chromosomes in the GnomAD database, including 5,606 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 (5606 hom., cov: 32)
• Consequence: ABCC11 NM_001370497.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 3 publications found

Genes affected

ABCC11 (HGNC:14639): (ATP binding cassette subfamily C member 11) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370497.1. 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
	ABCC11	NM_001370497.1	MANE Select	c.2083-350T>C		intron	N/A	NP_001357426.1
	ABCC11	NM_001370496.1		c.2083-350T>C		intron	N/A	NP_001357425.1
	ABCC11	NM_032583.4		c.2083-350T>C		intron	N/A	NP_115972.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	ENST00000356608.7	TSL:1 MANE Select	c.2083-350T>C		intron	N/A	ENSP00000349017.2
	ABCC11	ENST00000394747.5	TSL:1	c.2083-350T>C		intron	N/A	ENSP00000378230.1
	ABCC11	ENST00000394748.5	TSL:1	c.2083-350T>C		intron	N/A	ENSP00000378231.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38168 AN: 151698 Hom.: 5587 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0317

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38227 AN: 151814 Hom.: 5606 Cov.: 32 AF XY: 0.247 AC XY: 18350 AN XY: 74190

African (AFR) AF: 0.395 AC: 16298 AN: 41312

American (AMR) AF: 0.187 AC: 2861 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 807 AN: 3472

East Asian (EAS) AF: 0.0317 AC: 164 AN: 5166

South Asian (SAS) AF: 0.0782 AC: 377 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2303 AN: 10490

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14726 AN: 67962

Other (OTH) AF: 0.237 AC: 498 AN: 2104

Alfa AF: 0.230 Hom.: 6379

Bravo AF: 0.255

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-0.12
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: rs7203695; hg19: chr16-48232536;