9-104781415-TAAC-T

Variant names:

• chr9-104781415-TAAC-T
• rs41474449
• NM_005502.4:c.*2897_*2899delGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005502.4(ABCA1):​c.*2897_*2899delGTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,524 control chromosomes in the GnomAD database, including 1,187 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1187 hom., cov: 31)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: ABCA1 NM_005502.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 4 publications found

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-104781415-TAAC-T is Benign according to our data. Variant chr9-104781415-TAAC-T is described in ClinVar as [Benign]. Clinvar id is 1287228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.*2897_*2899delGTT		3_prime_UTR_variant	Exon 50 of 50	ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.960-6199_960-6197delCAA		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.*2897_*2899delGTT		3_prime_UTR_variant	Exon 50 of 50	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.*2897_*2899delGTT		3_prime_UTR_variant	Exon 50 of 50			ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16904 AN: 151974 Hom.: 1183 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0602 AC: 26 AN: 432 Hom.: 0 AF XY: 0.0385 AC XY: 10 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0610 AC: 26 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.111 AC: 16936 AN: 152092 Hom.: 1187 Cov.: 31 AF XY: 0.112 AC XY: 8310 AN XY: 74352

African (AFR) AF: 0.145 AC: 6025 AN: 41480

American (AMR) AF: 0.193 AC: 2944 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1298 AN: 5172

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4826

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5263 AN: 67950

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.101 Hom.: 110

Bravo AF: 0.127

Asia WGS AF: 0.143 AC: 497 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
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: rs41474449; hg19: chr9-107543696; COSMIC: COSV66063436; COSMIC: COSV66063436;