6-34246091-A-G

Variant names:

• chr6-34246091-A-G
• rs1150782
• NM_145899.3:c.*1207A>G

Variant summary

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

The ENST00000311487.9(HMGA1):​c.*1207A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 152,290 control chromosomes in the GnomAD database, including 73,542 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 0.98 (73542 hom., cov: 33)
  • Exomes 𝑓: 0.99 (42304 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGA1 ENST00000311487.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 3 publications found

Genes affected

HMGA1 (HGNC:5010): (high mobility group AT-hook 1) This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]

HMGA1 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000311487.9. 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
	HMGA1	NM_145899.3	MANE Select	c.*1207A>G		3_prime_UTR	Exon 6 of 6	NP_665906.1
	HMGA1	NM_001319078.2		c.*1207A>G		3_prime_UTR	Exon 5 of 5	NP_001306007.1
	HMGA1	NM_001319079.2		c.*1207A>G		3_prime_UTR	Exon 6 of 6	NP_001306008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA1	ENST00000311487.9	TSL:1 MANE Select	c.*1207A>G		3_prime_UTR	Exon 6 of 6	ENSP00000308227.4
	HMGA1	ENST00000447654.5	TSL:1	c.*1207A>G		3_prime_UTR	Exon 5 of 5	ENSP00000399888.1
	HMGA1	ENST00000347617.10	TSL:1	c.*1207A>G		3_prime_UTR	Exon 5 of 5	ENSP00000288245.9

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149516 AN: 152172 Hom.: 73486 Cov.: 33

Gnomad AFR AF: 0.949

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.977

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.994 AC: 85103 AN: 85624 Hom.: 42304 Cov.: 0 AF XY: 0.995 AC XY: 40421 AN XY: 40640

African (AFR) AF: 0.951 AC: 3168 AN: 3330

American (AMR) AF: 0.985 AC: 3358 AN: 3408

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 4508 AN: 4610

East Asian (EAS) AF: 1.00 AC: 10338 AN: 10338

South Asian (SAS) AF: 0.999 AC: 2816 AN: 2818

European-Finnish (FIN) AF: 1.00 AC: 916 AN: 916

Middle Eastern (MID) AF: 0.991 AC: 444 AN: 448

European-Non Finnish (NFE) AF: 0.998 AC: 52958 AN: 53076

Other (OTH) AF: 0.988 AC: 6597 AN: 6680

GnomAD4 genome AF: 0.983 AC: 149630 AN: 152290 Hom.: 73542 Cov.: 33 AF XY: 0.983 AC XY: 73216 AN XY: 74462

African (AFR) AF: 0.949 AC: 39428 AN: 41550

American (AMR) AF: 0.984 AC: 15069 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3387 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10623 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67864 AN: 68016

Other (OTH) AF: 0.978 AC: 2063 AN: 2110

Alfa AF: 0.998 Hom.: 80296

Bravo AF: 0.979

Asia WGS AF: 0.997 AC: 3466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.57
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: rs1150782; hg19: chr6-34213868;