rs2239320

Variant names:

• chr16-16212071-A-G
• rs2239320
• NM_001171.6:c.662+114T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-16212071-A-G
• chr16-16212071-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001171.6(ABCC6):​c.662+114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.043 (198 hom., cov: 22)
  • Exomes 𝑓: 0.00022 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 0 publications found

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) 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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ABCC6 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
• inherited pseudoxanthoma elasticum

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105371100 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. 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
	ABCC6	NM_001171.6	MANE Select	c.662+114T>C		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.662+114T>C		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.662+114T>C		intron	N/A	NP_001427239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.662+114T>C		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.662+114T>C		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.662+114T>C		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 4179 AN: 97134 Hom.: 197 Cov.: 22

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.0464

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0607

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0581

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000224 AC: 138 AN: 615652 Hom.: 11 AF XY: 0.000244 AC XY: 80 AN XY: 327512

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000777 AC: 9 AN: 11590

American (AMR) AF: 0.000200 AC: 7 AN: 34948

Ashkenazi Jewish (ASJ) AF: 0.000112 AC: 2 AN: 17778

East Asian (EAS) AF: 0.000868 AC: 21 AN: 24198

South Asian (SAS) AF: 0.000130 AC: 8 AN: 61714

European-Finnish (FIN) AF: 0.000104 AC: 5 AN: 48254

Middle Eastern (MID) AF: 0.00105 AC: 3 AN: 2868

European-Non Finnish (NFE) AF: 0.000195 AC: 75 AN: 384390

Other (OTH) AF: 0.000267 AC: 8 AN: 29912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0430 AC: 4175 AN: 97158 Hom.: 198 Cov.: 22 AF XY: 0.0396 AC XY: 1897 AN XY: 47860

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0789 AC: 1428 AN: 18100

American (AMR) AF: 0.0357 AC: 383 AN: 10716

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 107 AN: 2394

East Asian (EAS) AF: 0.103 AC: 276 AN: 2680

South Asian (SAS) AF: 0.0482 AC: 158 AN: 3278

European-Finnish (FIN) AF: 0.0129 AC: 114 AN: 8830

Middle Eastern (MID) AF: 0.0556 AC: 11 AN: 198

European-Non Finnish (NFE) AF: 0.0325 AC: 1591 AN: 48986

Other (OTH) AF: 0.0576 AC: 79 AN: 1372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.232 Hom.: 744

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2239320;

hg19: chr16-16305928;